Announcements

1 May 2021

2021 CDKL5 Pilot Grant Programme Awardees

Loulou Foundation is pleased to announce the six Awardees of the 2021 CDKL5 Pilot Grant Programme. Now in its sixth year, the CDKL5 Pilot Grant Programme is directed by the Loulou Foundation through its collaboration with the CDKL5 Program of Excellence at the Orphan Disease Center of the University of Pennsylvania Perelman School of Medicine.

The goal of the Programme is to advance basic and translational research on CDKL5 Deficiency Disorder (CDD), a rare neurodevelopmental disorder affecting thousands of patients around the world. Once again this year, the one-year research proposals submitted by these Pilot Grant Awardees cover a range of translational science topics, from the basic biology of CDKL5 to translational and clinical development of therapeutics for CDD.

Loulou Foundation congratulates the successful 2021 awardees and is grateful to all applicants to this year’s grant program for providing a high quality and competitive pool of research projects, as well as to the more than twenty scientists who served as peer reviewers for this year’s grant cycle, giving generously of their time and expertise to carefully evaluate all invited applications.


  2021 Pilot Grant Awardees:

Michela Fagiolini, PhD
Boston Children's Hospital, Boston, MA USA
“ASO therapy in CDKL5 deficiency disorder”

Victor Faundez, PhD
Emory University, Atlanta, GA USA
“Systems Analysis of the CDKL5-Deficiency Disorder (CDKL5-DD) Cerebrospinal Fluid Proteome”

Michael J. Higley, MD, PhD
Yale University, New Haven, CT USA
“Impact of Cdkl5 deficiency on cortical dynamics and network architecture”

Peter K. Jackson, PhD
Stanford University School of Medicine, Stanford, CA USA
“Defining ciliary signaling and targets in CDKL5 Deficiency Disorder”

Christopher McGraw, MD, PhD
Boston Children's Hospital, Boston, MA USA
“Advancing a mosaic CDKL5 zebrafish model for high-throughput screening approaches”

Dolan Sondhi, PhD
Weill Cornell Medicine, New York, NY USA
“Comparison of Brain Biodistribution of Two CDKL5 Gene Therapy Vector Leads”


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28 February 2021

Loulou Foundation featured in the RARE Revolution MENA and GCC region Spotlight edition

We are delighted to announce that we have been featured in the RARE Revolution MENA and GCC region Spotlight edition online magazine in honour of Rare Disease Day! Thank you for so generously covering our center’s work and accomplishments.

Read full article here

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3 February 2021

2021 CDKL5 Program of Excellence Pilot Grant Request for Application now available

The Loulou Foundation, in collaboration with the Orphan Disease Center (ODC) at the University of Pennsylvania, is pleased to announce the 2021 CDKL5 Program of Excellence Pilot Grant Program. CDKL5 Deficiency Disorder (CDD) is a monogenic, neurodevelopmental disorder characterized by treatment-resistant epilepsy and severe neurodevelopmental delay. The disease is driven by the loss of a kinase called CDKL5 which is responsible for normal neuronal development, synapse formation and signal transmission. The mechanisms by which loss of CDKL5 expression leads to this CNS disorder remain unclear. The gene encoding this protein is located on the X chromosome, with heterozygous females primarily affected. The disease does not exhibit neurodegeneration, and animal models strongly suggest the potential for reversibility. There are no approved therapies and standard of care is not effective at managing seizures or improving neurodevelopmental or motor deficits.

We are seeking grant applications that progress the discovery or development of treatments and/or cures for CDKL5 Deficiency Disorder. We recognize, however, that many gaps exist in the basic understanding of CDKL5 and its role in neurological development. Therefore, basic science projects that address these gaps are welcome, provided that they are tethered to the development of a potential therapy. The 2021 CDKL5 Pilot Grant Program Request for Applications (RFA) can be found here. While the RFA is broad in scope, priority will be given to grants that cover the following areas:

  1. Novel therapeutic approaches for CDD
  2. Validation of phenotypes in CDKL5 function or disease pathophysiology
  3. Systems biology and computational modeling approaches
  4. Novel application of imaging and functional techniques
  5. Discovery and validation of CDKL5 biomarkers

Letters of Interest (LOIs) are due no later than FRIDAY, FEBRUARY 26, 2021, by 5pm EST. Grant criteria, the entire RFA, and additional program details can be found here.

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2 May 2020

2020 CDKL5 Pilot Grant Programme Awardees

The Loulou Foundation is pleased to announce the eight Awardees of the 2020 CDKL5 Pilot Grant Programme, through its collaboration with the CDKL5 Program of Excellence at the Orphan Disease Center of the University of Pennsylvania Perelman School of Medicine.  The one-year research plans proposed by these first-time Pilot Grant Awardees cover a broad spectrum of translational science topics relevant to CDKL5 Deficiency Disorder, a rare neurodevelopmental disorder affecting thousands of patients across the world.  We thank all applicants, who provided a high quality and competitive pool of research projects to evaluate, as well as the scientists who gave their time as peer reviewers of all invited applications.


   2020 Pilot Grant Awardees:

Alan Brown, PhD
Harvard Medical School
“Visualizing the effect of CDKL5 deficiency on ciliary core structures”

Liqin Cao, PhD
Tsukuba University
“Elucidate the neural mechanisms underlying sleep disturbances and the relation between seizures and sleep-wake cycle in CDKL5 deficiency disorder (CDD)”

Simone DiGiovanni, MD, PhD
Imperial College London
“Characterization and correction of Cdkl5 nuclear function in human CDD neurons during maturation”

Maolin Guo, PhD
University of Massachusetts, Dartmouth
Incorporation of functional unnatural amino acids into CDKL5 to study its function in cells”

Steven A. McCarroll, PhD
Harvard Medical School
“Ascertaining the cell-autonomous effects of CDKL5 mutations in every brain cell type

Lauren Orefice, PhD
Massachusetts General Hospital
Assessing peripheral sensory neuron dysfunction in animal models for CDKL5 deficiency disorder”

Gregory J. Pazour, PhD
University of Massachusetts Medical School
CDKL5 regulation of ciliary assembly and signaling”

Maria Luisa Tutino, PhD
University of  Naples
Structural/functional characterization of full-length hCDKL5 isoform 1 produced in recombinant marine bacteria and use of pharmacological chaperones to stabilize hCDKL5 missense mutants”


Loulou Foundation would like to thank all those who applied to the programme, which led to a high quality of proposals.


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27 January 2020

Rare disease CDKL5 Deficiency Disorder granted WHO disease classification

  • The WHO disease classification will now include a disease called CDKL5 Deficiency Disorder.
  • CDKL5 Deficiency Disorder diagnostic code will be incorporated in the classification revision to be published on October 1, 2020.
  • The unique ICD-10 code will facilitate clinical and epidemiological research and improve patient care.

The rare genetic disease CDKL5 Deficiency Disorder (CDD) has been designated with a new disease code in the International Classification of Diseases (ICD), the medical classification list from the World Health Organization (WHO). The CDKL5 Deficiency Disorder diagnostic code will be incorporated in the October 1, 2020 classification revision.

The medical classification, currently in its tenth revision (ICD-10), uses a list of alphanumeric codes to document a person’s medical condition. For example, a person with migraine headaches will receive the G43 code, and a person with type 2 diabetes the E11 code. These codes are then used for clinical research and care, and increasingly also for health insurance billing and reimbursement. According to the WHO, about 70% of the world’s health expenditures are allocated using ICD codes for reimbursement and resource allocation.

There are many medical conditions that do not have a code in the international medical classification, and these diseases can be invisible for most clinical research and have difficulties accessing insurance and reimbursement.

This previously included CDD, a rare genetic disease that leads to frequent seizures shortly after birth and severe impairment in neurological development, with most affected people being unable to walk, talk or care for themselves.

“Obtaining an ICD-10 code for CDD is a big milestone for our field and one more step towards having approved therapies and ensuring patient access to these treatments said Ana Mingorance PhD, Chief Development Officer at the Loulou Foundation, a private non-profit foundation for CDD therapeutic development which spearheaded the ICD-10 code effort. “One of the reasons why we requested a code for CDD is because there are four ongoing clinical trials for therapies that might treat the disease, including a clinical study in the latest stage before approval. With an ICD-10 code for CDD, everything from research to reimbursement will become more efficient.”

“We know that CDD occurs in approximately 1 in every 40,000 births because of genetic studies”, explains Karen Utley, co-founder and President of the International Foundation for CDKL5 Research (IFCR), the largest patient advocacy group for CDD families in the United States. “But because there was no ICD-10 code for the disease, each of these patients is being coded in a different way at hospitals and we have no way to identify who they are or to know how many are out there”.

ICD-10 codes are used by clinicians, health insurance companies, and public health agencies across the world to represent diagnoses. The disease classification is reviewed once a year, in a process managed by the National Center for Health Statistics (NCHS), housed within the Centers for Disease Control and Prevention.

Last year, IFCR and the Loulou Foundation submitted a proposal to the NCHS for the creation of a new unique code for CDKL5 Deficiency Disorder. “The existing ICD-10 codes were not specific enough to capture the multisystem effects of CDD,” said Dr Eric Marsh from the Children’s Hospital of Philadelphia, one of the leading clinical investigators in the disorder and the Principal Investigator at the CDKL5 clinical Center of Excellence who also participated in the proposal. “This leads to the inconsistent records and introduces friction into clinical care, insurance authorization and research studies, all of which depend on ICD-10 codes.”

The proposal included support letters from numerous medical organizations including the American Epilepsy Society, American Academy of Neurology, and the Child Neurology Foundation, as well as from leading patient advocacy organizations like the National Organization for Rare Diseases. Several pharmaceutical companies also contributed support letters.

Following the evaluation, CDD was successfully granted a new code (G40.42), in an acknowledgment that it represents a separate medical condition with unique medical needs and that it therefore required its own ICD-10 code.

This milestone follows another major achievement for the CDD patient community, which on November 1, 2019, hosted a Patient-Focused Drug Development meeting with the FDA, in which caregivers shared their experience and future treatment expectations with the regulators.

The Loulou Foundation, IFCR, and the International CDKL5 Alliance, representing worldwide CDD patient advocacy groups, believe that the new ICD-10 code for CDD will help improve the quality of life of people living with CDD, and urge the medical community and healthcare leaders to advance policies and protocols to ensure early access to genetic diagnosis that will identify currently undiagnosed cases of this disorder.


About CDD

CDKL5 Deficiency Disorder (CDD) is a rare neurodevelopmental disorder resulting from loss-of-function mutations in the CDKL5 gene.  Presenting first as infantile spasms within the first weeks of life which progresses to intractable epilepsy, CDD patients also display profound neurodevelopmental delay, with generalized hypotonia, impaired motor skills, and severely impaired speech and vision.  CDD patients also have impaired sleep, gastrointestinal function, and respiratory issues.  With an incidence of approximately 1 in 40,000 live births, CDD is one of the most common monogenic pediatric epilepsies, with several thousand patients estimated in the US and Europe alone.  No therapies exist to treat the neurodevelopmental symptoms of CDD, and the epilepsy associated with CDD is poorly managed by current anti-seizure medications.


About Loulou Foundation

Loulou Foundation is a private, non-profit foundation dedicated to therapeutic development for CDD.  Founded in 2015, Loulou Foundation drives pre-clinical, translational, and clinical research on transformative therapeutics for CDD, with the goal of delivering meaningful treatments and eventual cures for CDD to patients and their families.

www.louloufoundation.org


About International Foundation for CDKL5 Research (IFCR)

IFCR is the largest US-based patient advocacy group for patients and families living with CDD.  Founded in 2009 by families with members living with CDD, IFCR is dedicated to improving the lives of CDD patients and families, through education and research programs.  IFCR has pioneered the establishment and development of CDD clinical centers of excellence at medical centers across the United States, to provide the highest quality, multi-disciplinary care for CDD patients and their families.

www.cdkl5.com


About the CDKL5 Alliance

The CDKL5 Alliance is the international network of patient advocacy groups for CDKL5 Deficiency Disorder (CDD), comprising organizations from 18 different nations on four different continents.  The role of the CDKL5 Alliance is to provide rapid communication and coordination between the different CDD patient advocacy groups, to support each other and share best practices in CDD education and clinical research and care.

www.cdkl5alliance.org


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3 December 2019

EMA grants its first Orphan Drug Designation for CDKL5 Deficiency Disorder

We would like to share with you the news that the European Medicines Agency (EMA) has granted its first Orphan Drug Designation for the treatment of CDKL5 Deficiency Disorder (CDD). The designation was granted to ganaxolone, in development by Marinus Pharmaceuticals.

Ganaxolone is currently being evaluated in Phase 3 clinical trials in CDD. The drug candidate is a positive allosteric modulator of the neuronal GABAA receptors in development for the treatment of drug-resistant seizures and psychiatric disorders.

Marinus had already been granted Orphan Drug Designation for ganaxolone by the FDA in 2017. These designations are a label granted by the regulatory agencies to experimental drugs that intend to treat a rare condition, defined as those affecting fewer than 200,000 people in the US or less than 5 in 10,000 people in the EU. The designation provides the sponsor with various drug development incentives, including 7 years of US market exclusivity and 10 years of EU market exclusivity after drug approval.

This is a significant step in the road towards better treatments and cures for CDD. While the FDA has already granted two Orphan Drug Designations to treatments in development for CDD (ganaxolone in 2017 and balipodect, from Takeda Pharma, in 2019) this is the first Orphan Drug Designation that the European regulator grants for the disorder. With this designation, the EMA recognizes that CDD is a unique disorder not adequately treated by currently available medications, which is one of the conditions for granting Orphan Drug Designations.

Although there is currently no drug approved for the treatment of CDD, there are four therapies in clinical trials. The most advanced clinical program is the ganaxolone trial, called the Marigold Study, which Marinus recently announced remains on-track to report top-line data in Q3 2020.


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29 October 2019

Loulou Foundation and Baylor College of Medicine-Texas Children’s Hospital announce joint research collaboration on CDKL5 Deficiency Disorder therapeutics

CDKL5 Deficiency Disorder (CDD) is a devastating neurodevelopmental disorder caused by mutations in the CDKL5 gene. The Loulou Foundation, a private non-profit foundation dedicated to the development of novel therapeutics for CDD, and Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital have launched a joint research collaboration focused on therapeutic research for this disorder.

The work will focus on the behavioral pharmacology of novel small molecule and genetic methods to reverse the behavioral and molecular deficits in animal models of CDD. The research is expected to help advance both the basic science as well as the therapeutic research towards more effective symptomatic and disease-modifying treatments for CDD, a disorder characterized by neurodevelopmental delay and intractable epilepsy. With an incidence of approximately one in 42,000 live births, CDD is one of the most common monogenic pediatric epilepsy disorders.

Few treatment options are effective to manage the epilepsy in CDD patients, and there are no therapeutics for the neurodevelopmental delay. Potential treatments in development range from small molecule therapeutics to gene therapy and genome engineering approaches. The collaboration led by the leadership of the Loulou Foundation and Dr. Rodney Samaco, assistant professor of molecular and human genetics at Baylor College Medicine and the NRI, will provide a pipeline of animal models and behavioral assay platforms to rapidly and efficiently evaluate different models or therapeutic approaches for their validity and reproducibility.

“The Loulou Foundation is proud to be working with Dr. Samaco and BCM-NRI on this important collaborative effort,” said Dr. Daniel J. Lavery, Chief Scientific Officer at the Loulou Foundation. “The development of effective therapeutics for CDD patients will be greatly aided by the robust platform for behavioral pharmacology at the NRI, allowing us to benefit from the Institute’s world class expertise and industry-scale infrastructure.”

Dr. Huda Y. Zoghbi, professor of molecular and human genetics, a Howard Hughes Medical Institute investigator at Baylor and Director of the NRI states, “I am thrilled that the LouLou Foundation chose to support research aimed at testing therapeutics in preclinical models of CDKL5 at the NRI. This generous support will enable rigorous testing that we hope will help those with CDD.”

“As a team, the scale of this collaboration has the potential to alter the course of the therapeutic landscape,” Samaco said. “In the rare genetic disease space, there is overwhelming support to bring the ‘voice’ of all stakeholders to the decision-making platform. This initiative will provide significant and immediate impact to the CDD field, and possibly other rare disorders with overlapping features.”

Zoghbi is also professor of pediatrics, neuroscience, a member of the Dan L Duncan Comprehensive Cancer Center and the Ralph D. Feigin Professor at Baylor.



announcement

Signing of the joint research collaboration agreement between the Loulou Foundation, and the Jan and Dan Duncan Neurological Institute of Texas Children’s Hospital. Front row, left to right: Mrs Lynn Barghout Jafar, Co-Founder, Loulou Foundation; Prof Huda Zoghbi, Professor, Baylor College of Medicine, and Director, Jan and Dan Duncan Neurological Research Institute.

Back row, left to right: Dr Surabi Veeraragavan, Baylor College of Medicine; Mr Derek Reznik, Baylor College of Medicine; Dr Daniel Lavery, Chief Scientific Officer, LouLou Foundation; Mr Majid Jafar, Co-Founder, LouLou Foundation; Dr Rodney Samaco, Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute; Ms Miranda Torres, Baylor College of Medicine; and Dr Christopher McGraw, Massachusetts General Hospital.

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2 October 2019

New report shows rare disease more common than previously thought

  • Of all children with epilepsy which starts in the first 3 years of age, one in four are found to have a genetic syndrome
  • Mutations in the CDKL5 gene found to be one of the most common genetic causes of epilepsy in children
  • Previous estimates of a few hundreds of patients in the world with CDKL5 Deficiency Disorder, now replaced by estimates of over 10,000 cases

Approximately one in forty-two thousand children are born with a disease called CDKL5 Deficiency Disorder, according to a new medical report recently published in the journal Brain and presented last month at the 13th European Paediatric Neurology Society Congress in Athens, Greece. This means that each year there are over 100 new children born with the disease in the EU alone, and over 3,000 in the world.

The disease leads to frequent seizures shortly after birth and severe impairment in neurological development, with most affected people being unable to walk, talk or care for themselves. “When our daughter was diagnosed in 2009 they told us there were approximately 200 cases in the world”, says Carol-Anne Partridge, Chair of CDKL5 UK and the International CDKL5 Alliance, which represents patient organizations from 18 countries. “Today we know that these children were simply not being diagnosed correctly,” she adds.

The study, by a medical team from the Royal Hospital for Children in Glasgow, kept track of all births in Scotland during three years and applied genetic testing to all children under 3 years of age who developed epilepsy. “We found that as many as 1 in 4 children with epilepsy have a genetic syndrome”, explains Prof Sameer Zuberi, corresponding author for the study, “and a small group of genes explains most of the cases.”

Among these genes is CDKL5, which encodes a protein necessary for proper brain functioning. Mutations in the CDKL5 gene produce CDKL5 Deficiency Disorder, with one of the first symptoms being early-onset epilepsy. There is no therapy approved for treating the disease now known to affect thousands of people.

But therapies are being developed and the disease has recently attracted much interest from the pharmaceutical industry. There are four clinical trials currently ongoing, and additional companies have announced efforts towards the development of enzyme replacement and gene therapies.

The new disease incidence study highlights the need to increase disease awareness around these genetic disorders previously thought to be much more rare. “Our data suggest that genetic testing should be a primary investigation for epilepsies presenting in early childhood,” explains Prof Sameer Zuberi.

Most of these cases are due to de novo (spontaneous) mutations, so they can occur in any family. But genetic testing is not offered to many patients with early childhood epilepsy and neurodevelopmental disabilities. Because of that, only about 10% of all people living with CDKL5 Deficiency Disorder might have a correct diagnosis.

“These new incidence findings demonstrate that there is still much work to do to diagnose CDKL5 Deficiency Disorder correctly,” explains Daniel Lavery PhD, Chief Scientific Officer of the Loulou Foundation. “As we partner with pharmaceutical companies to develop new therapies and cures for the disorder, we also need to find the thousands of people that are living with this condition so that they can access these new therapies,” he adds.

There is a growing community of researchers from academia and industry with over 500 members working on CDKL5 Deficiency Disorder and organized under the CDKL5 Forum, a project of the Loulou Foundation. The Loulou Foundation also hosts the CDKL5 Forum annual meeting, with this year’s meeting taking place in Boston on November 4th and 5th. The International CDKL5 Alliance recently also held their annual meeting in Edinburgh, Scotland.

The Loulou Foundation and the International CDKL5 Alliance urge the medical community and healthcare leaders to advance policies and protocols to ensure early access to genetic testing to children and adults who experience epilepsy in early childhood.


Article: Joseph D Symonds, Sameer M Zuberi, et al., (2019), Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort, Brain, https://doi.org/10.1093/brain/awz195
Enquires/Media:
Daniel Lavery, PhD
Chief Scientist Officer, Louou Foundation
Director, CDKL5 Program of Excellence, Orphan Disease Center
Perelman School of Medicine
University of Pennsylvania
T: +1 (215) 746-6725
E: dlavery@louloufoundation.org

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06 May 2019

2019 CDKL5 Pilot Grant Programme Awardees

The Loulou Foundation is pleased to announce the six Awardees of the 2019 Pilot Grant Program through its collaboration with the CDKL5 Program of Excellence at the Orphan Disease Center of the University of Pennsylvania. These Awardees include four first-time awardees and two awards for Continuation Funding of previous Pilot Grant Awards. We thank all applicants, who provided a high quality and competitive pool of research projects to evaluate.


   2019 Pilot Grant Awardees:

Massimiliano Bianchi, PhD
Trinity College Dublin
“Plasma microtubule proteins as potential biomarkers for CDKL5 Deficiency Disorder (CDD)”

Victor Faundez, PhD
Emory University
“CDKL5-Deficiency Disorder (CDKL5-DD) Biomarkers Discovery Through System Biology”

Teruyuki Tanaka, PhD
University of Tokyo
“Identifying the brain-wide, synapse-to-circuit functional abnormalities upon the loss of CDKL5 kinase activity in ubiquitous/excitatory/inhibitory-neuron-specific Cdkl5 kinase-dead knock-in mice and human patients”

Cleber A. Trujillo, PhD
University of California, San Diego
“High-throughput drug screening platform for CDD cortical organoids”


   Continuation Funding Awardees:

Alysson Muotri, PhD
University of California, San Diego
"CDKL5 Syndrome cortical organoids for drug testing and reversibility potential" (2017)

David Liu, PhD
“Development of Targeted Frameshifting Technologies” (2018)

 

Loulou Foundation would like to thank all those who applied to the programme, which led to a high quality of proposals.

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8 April 2019

New clinical review of CDKL5 Deficiency Disorder published

We would like to share with you the most recent review published about CDKL5 Deficiency Disorder (CDD) by an international team of clinical key opinion leaders.

The article is currently in press at Pediatric Neurology: https://www.pedneur.com/article/S0887-8994(19)30012-8/abstract

The CDD field has seen rapid progress in the recent years and so a new clinical review is indeed timely. Among some key points that are highlighted in the paper:

  • More recent incidence estimates for CDD are 1 in 40-60,000 live births.
  • CDD is clearly a separate disorder from Rett syndrome.
  • Epilepsy usually begins in the first three months of life and includes tonic seizures, epileptic spasms without hypsarrhythmia, a seizure-free honeymoon period around one to two years old that may last up to 12 months, followed by multiple seizure types including sequences of mixed seizure type. 80% of patients experience daily seizures, with the remaining 20% weekly to monthly.
  • A summary of response to anti-epileptic medications is given. It is common to use broad-spectrum anti seizure medications in combination.
  • All individuals with CDD have severe cognitive and developmental delays, hypotonia and movement disorders. 75% of individuals also have cortical visual impairment. Gastrointestinal symptoms and sleep difficulties are also common.
  • There are multiple drug development programs ongoing, including positive Phase 2 data from Epidiolex (open-label) and ongoing clinical trials with ganaxolone. The expert clinicians propose a minimum CDD diagnostic criteria of “pathogenic or likely pathogenic variant in the CDKL5 gene along with motor and cognitive developmental delays and epilepsy with onset in the first year of life”.

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24 January 2019

Collaboration with Abcam Plc

The Loulou Foundation is pleased to announce the launch of a collaboration with Abcam Plc to create critical reagents for the advancement of research on CDKL5 deficiency disorder (CDD). Using Abcam’s proprietary rabbit monoclonal antibody platform, the collaboration will generate high quality monoclonal antibodies capable of detecting distinct domains on the CDKL5 protein, as well as detecting phosphorylation of a serine residue on Map1S protein that has been shown to be a target of the CDKL5 kinase.

Once generated, these reagents will be available through Abcam for research and development to study all aspects of CDKL5 biology, from basic kinase mechanisms through validation of therapeutic approaches for the treatment and eventual cure for CDD.

More details on the collaboration can be found here, press release from Loulou Foundation and Abcam.

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25 October 2018

MAIN LESSONS FROM THE 2018 CDKL5 FORUM

For the past four years the Loulou Foundation hosts an annual “by invitation only” meeting where scientists and drug developers working on CDKL5 deficiency, together with representatives from patient organizations, meet to discuss the latest advances. This was the second Forum I attended, and my first since joining the Loulou Foundation.

There were major news announced during the meeting, like a new Phase 2 clinical trial in CDKL5 deficiency disorder with fenfluramine, a drug that has completed two Phase 3 clinical trials in Dravet syndrome with very strong efficacy, and the announcement that Ultragenyx will develop a gene therapy for CDKL5 deficiency disorder.

For those of you who didn’t attend but are interested in the field, here are the main news and take-home messages from the 2018 CDKL5 Forum that took place in London, UK, in October 22 and 23:

1. THE DEVELOPMENT OF THERAPIES FOR CDKL5 DEFICIENCY DISORDER HAS PROGRESSED VERY FAST

One of the CDKL5 researchers explained from the stage that 4 years ago there were only 20 publications on CDKL5. Four years later, he was standing in a room with nearly 200 scientists and drug developers, discussing 4 clinical trials. From what we know today about the pipeline, in 4 more years we might already have the first symptomatic drugs approved, and will be running clinical trials with the enzyme replacement therapy and gene therapy that are already in development. This speed of development in a rare disease is truly remarkable.

The Chief medical Officer of Marinus echoed these comments by reminding the audience that just a year ago they stood in front of the regulators discussing if “CDKL5 deficiency disorder” was truly a disease or simply a gene that can present as many different syndromes when mutated.  After the Loulou Foundation and the patient organizations mobilized and made sure that CDKL5 deficiency disorder was listed in the major disease classification websites and documented as the separate entity that it is, the FDA not only accepted the indication but also approved the first pivotal trial for this disease. We went from not having a recognized disorder to getting green light for a pivotal trial in a matter of weeks.

2. THERE IS A STRONG INDUSTRY INTEREST IN CDKL5 DEFICIENCY DISORDER

IMG_1216.jpg

In addition to Marinus Therapeutics, which is in the middle of recruiting for their Pivotal stage Phase 3 trial for CDKL5 deficiency disorder, there were 22 more companies in the room at the 2018 CDKL5 Forum. Last year meeting took place in Boston, and 35 companies attended, but I personally through that the majority would only be there because they have local offices and it was easy for anyone who was just mildly curious to drop by. Having 23 companies come to London means the interest goes beyond mere opportunistic curiosity, and that list of programs in development to treat CDKL5 deficiency disorder is likely to grow in the next few years as this interest materializes in development programs.

The Loulou Foundation honored the companies Takeda and Ovid Therapeutics during the Forum in recognition of their contribution to research and therapeutic development in CDKL5 deficiency disorder

The current pipeline for CDKL5 deficiency disorder has one drug in Phase 3 (pivotal) trials, and three drugs in Phase 2 (proof-of-concept) clinical trials:

Phase 3: Ganaxolone, from Marinus Therapeutics, currently enrolling through 40 clinical sites across EU and US. This is the only placebo-controlled pivotal trial requested for registration of the drug, so once completed Marinus should be able to file for marketing authorization. The company estimates to enroll 70 to 100 patients in total.

Phase 2: Ataluren, from PTC Therapeutics, currently completing a placebo-controlled investigator-initiated study at NYU Langone Medical Center in children with CDKL5 deficiency disorder caused by non-sense mutations. This study enrolled 9 patients.

Phase 2: OV935 (TAK-935), from Ovid Therapeutics in partnership with Takeda, currently enrolling for an open-label study through multiple sites in the US a total of 15 patients with CDKL5 deficiency disorder.

Phase 2: Fenfluramine, from Zogenix, soon to start enrolling for an open-label investigator-initiated study at NYU Langone Medical Center in children with CDKL5 deficiency disorder. This study will enroll 10 patients, and was announced for the first time at the CDKL5 Forum.

3. COMPANIES DEVELOPING CURE-LIKE TREATMENTS FOR CDKL5 DEFICIENCY DISORDER ARE MOVING FORWARD AGGRESSIVELY

Amicus recently announced a collaboration around a new AAV (gene therapy)-based technology to complement their enzyme-replacement therapy in development for CDKL5 deficiency disorder. With this new approach, they will use a virus to deliver a secretable form of the CDKL5 enzyme to brain of patients, so it can replace the missing endogenous enzyme.

The first day of the 2018 CDKL5 Forum meeting brought the groundbreaking news that Ultragenyx, one of the strongest players in the rare disease space, had reached an agreement with RegenXBio, one of the strongest players in gene therapy development, to develop a gene therapy approach for CDKL5 deficiency disorder.

With the strong interest that this rare disease is attracting, and its potential tractability by enzyme replacement and gene therapy approaches, we are likely to see the number of companies working in this space grow, and hopefully some clinical trials starting in a couple of years.

4. THE PRECLINICAL KNOWLEDGE AND PRECLINICAL TOOLBOX HAVE PROGRESSED MUCH

IMG_1191.jpg

We have progressed much in our understanding of the biology of CDKL5 and the consequences of the deficiency for cells and animals. One of the main breakthroughs of the past year has been the identification of some of the substrates of CDKL5, which were discovered in separate labs using different approaches and are therefore very solid findings. Interestingly, these key phosphorylation targets are cytoskeleton-binding proteins, which appears to be one of the main cellular domains where the kinase is important.

It was also encouraging to see that there are multiple mouse models generated for CDKL5 deficiency disorder, either missing the gene or carrying patient mutations, and that there are some solid phenotypes that are reproducible across labs and that can help carry out preclinical trials in the disorder. Interestingly, these mice don’t develop spontaneous seizures, but with four drugs in clinical trials for the disease using seizures as the primary efficacy endpoint this does not seem to be a problem for the pharmaceutical industry. The consensus in the room was that “a mouse is a mouse” and as long as the mice have clear neurological phenotypes that are driven by the deficiency in CDKL5 they are good models. The most anticipated experiment, the “rescue” experiment where expression of CDKL5 is turned back on in previously deficient mice, is about to start thanks to the creation of a conditional mouse model and the entire field awaits with expectation those results.

5. GETTING THE FIELD READY FOR MORE COMPLEX CLINICAL TRIALS

We also discussed during the Forum that although the first clinical trials in CDKL5 deficiency disorder are using seizure frequency as the primary efficacy endpoint, it is expected that future clinicals will measure more broadly the developmental disability of the disease and any potential improvement from treatment. Speakers from Ultragenyx and Roche explained how the industry approaches the development of new clinical outcomes and the importance of precompetitive collaborations in this space to move the field forward. The Loulou Foundation and IFCR (the US CDKL5 deficiency patient organization) are planning to host an externally-led PFDD meeting with the FDA in 2019 that will also assist with the identification of new meaningful clinical outcomes.

A captivating and inspirational Dr Emil Kakkis, from Ultragenyx and the EveryLifeFoundation, shared with the audience his journey to convince the industry that developing therapeutics for rare diseases was worth it, and some of his victories and approaches to turn these aspirations into a reality. He made a call for the use of multi-domain outcomes and biomarkers in clinical trials in rare populations, and why he thinks that the golden age of rare disease treatments is now coming to CDKL5 deficiency disorder.

“These are exciting times for rare diseases, and CDKL5 deficiency disorder is now front and center. Collaboration and cooperation is needed to identify the best outcomes as soon as possible. “

6. THERE IS A STRONG PATIENT COMMUNITY BEHIND CDKL5 DEFICIENCY DISORDER

The very young CDKL5 Alliance, the umbrella organization that groups 15 patient organizations and foundations, announced during the CDKL5 Forum the launch of their website with the hope of making it easier for any family around the globe to stay updated about progresses in the field and to connect with other patient families (http://www.cdkl5alliance.org).

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The CDKL5 Alliance met during the Forum and set some of their next priorities, including the identification of more patients and setting Centers of Excellence in every country so that the community is ready to run multiple clinical trials. They also receive the Champion of Progress 2018 award from the Loulou Foundation for building and keeping the community together.

During the Forum, the patient groups and the Loulou Foundation were credited with having been instrumental to the large progress in the field so far. From providing the key initial funding to research labs, to helping create Centers of Excellence and reaching out to companies to encourage them to consider their disorder and help them. Essentially, the secret for points 1 through 5 in this summary is the strong patient community behind CDKL5 deficiency disorder.

The patient groups and the Loulou Foundation have also managed to createa broader community where scientists and drug developers also find their home. This was particularly visible during the 2018 CDKL5 Forum where drug developers mixed with academic scientists and clinicals as speakers and moderators in the meeting, and where breakout sessions to help design the future of CDKL5 research sat around the table researchers, drug developers and patient parents without distinctions.

All in all this was a really good scientific meeting, with strong collaboration from all sectors in the CDKL5 community, and where it became clear that as Dr Kakkis said CDKL5 deficiency disorder is now front and center, and where we have a real opportunity to change the future of the disease.

Ana Mingorance, PhD


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11 October 2018

Announcement of 2018 CDKL5 Forum Junior Fellowship awardees

The CDKL5 Forum is pleased to announce the five awardees of the 2018 CDKL5 Forum Junior Fellowships.  These annual Fellowships recognize junior researchers who have already demonstrated a strong work ethic, a contribution to the field through an established track record, and a commitment to the CDKL5 Deficiency Disorder community.  Each Junior Fellowship carries an award of US$10,000 to the laboratory of which the awardee is a member, to directly support CDKL5 research.  All awardees are also invited to the 2018 CDKL5 Forum in London later this month, where they will be recognized.

In alphabetical order, the 2018 CDKL5 Forum Junior Fellowship awardees are:

  • Isabella Barbiero, PhD; Kilstrup-Nielsen laboratory, University of Insubria
  • Paul Baxter, PhD; Hardingham and Kind laboratories, University of Edinburgh
  • Priscilla Negraes, PhD; Muotri laboratory, University of California, San Diego
  • William Renthal, MD, PhD; Greenberg laboratory, Harvard Medical School
  • Madhumita Yennawar; Jensen laboratory, University of Pennsylvania

Many excellent nominations were received by the review committee for these competitive fellowships and we applaud the efforts of all these young researchers in their tireless efforts to advance the CDKL5 research agenda. We look forward to their ongoing contributions in furthering therapeutic development for CDKL5 Deficiency Disorder, for the benefit of all the patients and their families.

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11 June 2018

NIH Awards First R01 Grant for CDKL5 Study

The National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH) has just awarded a five-year R01 research grant, entitled “Pathogenic Studies of CDKL5 Disorder,” to Dr. Zhaolan (Joe) Zhou, Principal Investigator (PI), at the University of Pennsylvania Perelman School of Medicine, and Dr. Douglas Coulter, co-PI, at the University of Pennsylvania Perelman School of Medicine and Children’s Hospital of Philadelphia. This is the first R01-type research grant awarded by NIH to focus specifically on CDKL5 Deficiency Disorder (CDD). The grant will support Dr. Zhou to investigate the molecular and cellular functions of CDKL5 in defined neuronal populations where CDKL5 is highly expressed, and will support Dr. Coulter to interrogate the neural circuit mechanisms by which selective loss of CDKL5 in defined neurons leads to CDD-related behavioral phenotypes.

The foundation of this work, such as conditional knockout studies of CDKL5 in selective neuronal populations, was enabled by previous grant support from the Loulou Foundation and the International Foundation for CDKL5 Research (IFCR), also recognized by the 2017 CDKL5 Forum Lab of the Year Award to Zhou Lab this past November. This work has also led to an important publication in the Journal of Neuroscience (Tang et al., 2017). The generous sharing of knockout, conditional knockout, and knock-in mouse models bearing CDD-associated genetic mutations by Dr. Zhou has enabled multiple other studies on the mechanisms of behavioral and physiological deficits in mice lacking functional CDKL5 expression. These mouse models are currently available at The Jackson Laboratory without any restrictions.

The Loulou Foundation applauds this recognition by NINDS/NIH of the importance of supporting more research into CDKL5 Deficiency Disorder and of Dr. Zhou’s seminal work in creating and analyzing mouse models of CDD, and is proud that early support of this work by the Foundation has led to greater government grant support of one of our community’s key researchers. We hope this serves as an inspiration to other researchers who are working to better understand CDD and to advance basic and translational research leading to effective treatments and cures for our growing identified patient population.

 

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01 May 2018

2018 CDKL5 Pilot Grant Programme Awardees

Loulou Foundation is pleased to announce the seven Awardees of its 2018 Pilot Grant Program through the CDKL5 Program of Excellence at the Orphan Disease Center of the University of Pennsylvania:

Nicola Allen, PhD
Salk Institute for Biological Sciences
"Systems Level Analysis of CDKL5 Astrocytes to Identify Novel Markers and Pathways in CDKL5 Deficiency Disorder (CDD)"

Alessia DiNardo, PhD
Boston Children’s Hospital
"High Content Screen to identify drug targets for the neuronal manifestations of CDKL5 deficiency"

James Eubanks, PhD
University of Toronto
"Evaluating a Novel Strategy to Stimulate mTORC1 in Two Mouse Models of CDKL5 Deficiency Disorder"

Michela Fagiolini, PhD
Boston Children’s Hospital
"Testing functional and structural connectivity in CDKL5 deficiency disorder as novel biomarkers"

Michael Greenberg, PhD
Harvard Medical School
"Single-cell Transcriptional Profiling of Mosaic CDKL5 Deficiency Disorder Brain Tissue"

David Liu, PhD
Broad Institute and Harvard University
"Development of Targeted Frameshifting Technologies"

Ihn Sik Seong, PhD
Massachusetts General Hospital
"Quantitative SRM assays for optimization of CDKL5 protein replacement therapy"

Loulou Foundation would like to thank all those who applied to the 2018 program, which resulted in a record number of high quality proposals.

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27 February 2018

Ana Mingorance appointed as Chief Development Officer

The Loulou Foundation is pleased to announce that Ana Mingorance, PhD, has been appointed as Chief Development Officer.

Ana is a specialist in rare genetic syndromes and orphan drug development. She has worked both within the pharmaceutical industry and as a consultant to biotech and pharmaceutical companies. For the past 6 years she has used that knowledge to join forces with the Dravet syndrome patient community and help them accelerate the development of better treatments for Dravet syndrome.

Ana now brings all that experience to the Loulou Foundation to help us build partnerships with biotech and pharmaceutical companies, increase the number of programs in development to treat CDKL5 deficiency disorder, and get us closer to developing new treatments and cures.

She will be working closely with Dan Lavery the CSO of the Foundation, and can be reached on amingorance@louloufoundation.org.

 

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9 February 2018

2018 CDKL5 Grant Opportunity

The Orphan Disease Center (ODC) at the University of Pennsylvania and the Loulou Foundation are pleased to announce the 2018 Pilot Grant Program for CDKL5 Deficiency Disorder (CDD). CDD is a monogenic, orphan condition characterized by treatment-resistant epilepsy and severe cognitive and motor disability. The Loulou Foundation and the ODC will provide a one-year grant for $150,000.00 (total cost) to support research related to CDD – number of awards may vary.

We encourage you to review these application materials. Likewise, please share this funding opportunity with those holding a faculty-level appointment in your department, or other faculty who may be interested in this area of research. All applicants must first submit a letter of Interest (LOI) to be reviewed for consideration of a full application submission. LOIs are due no later than Thursday, March 8, 2018 at 5pm (EST). LOIs can be uploaded via this form, also found on our website. Full application guidelines including the Loulou Foundation Patent Policy are attached.

We are seeking grant applications that progress the discovery or development of treatments or cures for CDD. We recognize, however, that many gaps exist in the basic understanding of CDKL5 and its role in neurologic development. Therefore, basic science projects that address these gaps are welcome, as long as they are tethered to the development of a potential therapy. While the RFA is broad in scope, priority will be given to grants that cover the following areas:

  1. Novel therapeutic approaches for CDKL5 Deficiency Disorder (CDD), including but not limited to techniques in genome editing, RNA-based mechanisms, biologics, and small molecule repurposing.
  2. Approaches to validate phenotypes in CDKL5 function or disease pathophysiology through rescue of phenotypic deficits with pharmacological or genetic / gene therapy techniques. Phenotypic reversal in rodent models will focus on the use of adult (2 months of age or older) animals. In particular, approaches are encouraged which allow the identification of individual CDKL5 protein isoforms (arising from alternative splicing, alternative promoter usage, or post-translational modifications) which can rescue these phenotypes.
  3. Systems biology and computational modeling approaches to provide a deeper understanding of CDKL5 function, downstream effectors, signaling, protein:protein interactors, or modifiers, including regulators of CDKL5 gene expression (transcriptional, post-transcriptional/RNA processing, translational, post-translational).
  4. Novel imaging and functional approaches to phenotyping CDD in pre-clinical models or the clinical setting. A non-exclusive list of topics that would be responsive to this RFA is listed below:
    • Functional/structural MRI; diffusion tensor imaging (DTI)
    • Magnetic resonance spectroscopy (MRS)
    • Stimulus-induced event-related potentials: impact of CDKL5 genetic / gene therapy or pharmacological interventions on deficits in stimulus-induced event potentials (visual, auditory, or other) in CDD disease models
  5. Discovery and validation of CDKL5 biomarkers and their translation to the clinical.

 

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08 October 2017

2017 CDKL5 Forum Meeting - Boston, November 29-30

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The 2017 CDKL5 Forum, the flagship meeting on discovery and therapeutic research on CDKL5 deficiency disorder, will be held 29-30 Nov 2017 at the Royal Sonesta Hotel in Cambridge MA, USA.  The Forum, the leading scientific conference dedicated solely to therapeutic development for CDKL5 deficiency disorder, is organized by the Loulou Foundation, in collaboration with the Orphan Disease Center at the University of Pennsylvania’s Perelman School of Medicine.

Now in its third year, the Forum assembles, by invitation, scientists, clinicians, and drug discovery experts from around the world for presentations, panel discussions, breakout sessions, and poster presentations on all topics relating to CDKL5 biology and therapeutic development.  For the first time, the Forum is being held in Cambridge, MA, the dynamic epicenter of innovative biotechnology and therapeutic research.

Building on the successes of the last two years, the Forum has already exceeded registration from the previous events, and includes representatives from over 60 different academic, non-profit, and biotech/pharma institutions from four continents.  With recent exciting developments in pre-clinical and clinical research, this year’s Forum promises to highlight the advances made in the community in the past year, and set the agenda for even more progress in the immediate future.

A summary of the proceedings from the 2017 Forum will be made available after the conclusion of the conference, and will be accessible on both the Loulou Foundation website (https://www.louloufoundation.org) and the CDKL5 Forum portal (https://www.CDKL5forum.org).

 

 

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8 Aug 2017

FDA Grants Orphan Drug Designation for Ganaxolone in CDKL5 Disorder

RADNOR, Pa., June 29, 2017 (GLOBE NEWSWIRE) — Marinus Pharmaceuticals, Inc. (Nasdaq:MRNS), a biopharmaceutical company dedicated to the development of innovative therapeutics to treat epilepsy and neuropsychiatric disorders, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to ganaxolone for the treatment of CDKL5 Disorder. Ganaxolone is currently being evaluated in children with CDKL5 Disorder in a Phase 2 clinical trial.

“CDKL5 Disorder is a severe, rare genetic disorder that affects children at an early age and causes difficult-to-control seizures and neuro-developmental impairment,” remarked Christopher M. Cashman, Chief Executive Officer of Marinus Pharmaceuticals. “There are no approved therapies for children with CDKL5 Disorder, and a great need for new treatment options that can control both the seizures and co-morbidities of the disease to improve the quality of life for the child and their family.  We are pleased to receive Orphan Drug Designation for ganaxolone in CDKL5 Disorder and look forward to presenting the data from our ongoing Phase 2 trial in the upcoming months.”

Orphan Drug Designation is granted by the FDA Office of Orphan Products Development to novel drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 patients in the U.S. The designation provides the drug developer with a seven-year period of U.S. marketing exclusivity, as well as tax credits for clinical research costs, the ability to apply for annual grant funding, clinical research trial design assistance and waiver of Prescription Drug User Fee Act (PDUFA) filing fees.

About CDKL5 Disorder

CDKL5 Disorder is a serious and rare genetic disorder that is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. It predominantly affects girls and is characterized by early-onset, difficult-to-control seizures and severe neuro‑developmental impairment. The CDKL5 gene encodes a protein essential for normal brain function.  Most children affected by CDKL5 cannot walk, talk, or care for themselves. Many also suffer from scoliosis, visual impairment, gastrointestinal difficulties, and sleeping disorders. Currently, there are no approved therapies for CDKL5 Disorder.

About Ganaxolone

Ganaxolone, a positive allosteric modulator of GABAA, is being developed in three different dose forms (intravenous, capsule, and liquid) intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Unlike benzodiazepines, ganaxolone exhibits anti-seizure and anti-anxiety activity via its effects on synaptic and extrasynaptic GABAA receptors.  Ganaxolone has been studied in more than 1,500 subjects, both pediatric and adult, at therapeutically relevant dose levels and treatment regimens for up to two years. In these studies, ganaxolone was generally safe and well-tolerated. The most commonly reported adverse events were somnolence, dizziness and fatigue.

About Marinus Pharmaceuticals

Marinus Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to the development of ganaxolone, which offers a new mechanism of action, demonstrated efficacy and safety, and convenient dosing to improve the lives of patients suffering from epilepsy and neuropsychiatric disorders. Ganaxolone is a positive allosteric modulator of GABAA that acts on a well-characterized target in the brain known to have both anti-seizure and anti-anxiety effects. Ganaxolone is being developed in three different dose forms (IV, capsule and liquid) intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Marinus is currently evaluating ganaxolone in women with PPD and in orphan pediatric indications for the treatment of genetic seizure and behavior disorders, and preparing to initiate Phase 2 studies in status epilepticus, an orphan indication. For more information visit https://www.marinuspharma.com/. Please follow us on Twitter: @MarinusPharma.

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5 May 2017

CDKL5 Pilot Grant Programme Awardees 2017

Loulou Foundation (LLF) is pleased to announce the ten successful Awardees of its 2017 Pilot Grant Program through the CDKL5 Programme of Excellence (PoE) at the Orphan Disease Center (ODC) of the University of Pennsylvania:

Timothy Benke, MD, PhD
University of Colorado
"Mechanisms and treatment of paradoxical hyperexcitability in CDKL5 Deficiency Syndrome"

Elisabetta Ciani, PhD
University of Bologna
"Innovative Strategy to Enhance the Efficiency of Gene Therapy for CDKL5 Disorder"

Vera Kalscheuer, PhD
Max Planck Institute for Molecular Genetics
"Novel CDKL5 complex partners and kinase substrate candidates"

Charlotte Kilstrup-Nielsen, PhD
University of Insurbia
"Therapeutic potential of pregnenolone and its synthetic non-metabolized derivative for CDKL5 disorder"

Alysson Muotri, PhD
University of California San Diego
"CDKL5 Syndrome cortical organoids for drug testing and reversibility potential"

Tommaso Pizzorusso, PhD
Institute of Neuroscience, CNR
"Rescuing CDKL5 mice phenotype by targeting developmental critical period mechanisms"

David Rowitch, MD, PhD
University of Cambridge
"Understanding CDKL5 Expression Pattern by RNAScope in Developing Mouse and Human Glia"

W Andy Tao, PhD
Purdue University
"Identification of CDKL5 direct substrates based on kinase assay linked phosphoproteomics"

Sila Ultanir, PhD
The Francis Crick Institute
"Development of biomarkers for CDKL5 activity"

Robert Wilson, MD, PhD
University of Pennsylvania and the Children's Hospital of Philadelphia
"Therapeutic drug discovery for CDKL5 deficiency using random shRNA selection"

Loulou Foundation would like to thank all those who applied to the programme, which led to a high quality of proposals.

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22 March 2017

Loulou Foundation joins IRDiRC as new member

The Loulou Foundation, a private, non-profit UK foundation dedicated to advancing research into the understanding and development of therapeutics for CDKL5 deficiency disorder, has joined International Rare Diseases Research Consortium (IRDiRC) as new funding agency. Next to funding research, the Loulou Foundation places a high priority on partnering with the biopharma industry.

The International Rare Diseases Research Consortium (IRDiRC) brings together members that share common goals and principles and have agreed to work in a collaborative manner within a multinational consortium. IRDiRC teams up researchers and organizations investing in rare diseases research to achieve two main objectives by the year 2020, namely to deliver 200 new therapies for rare diseases and the means to diagnose most rare diseases.

Members are:

  • Funding organizations spending more than 10 million USD over 5 years in research projects contributing to IRDiRC objectives
  • Government, academia, industry and patient organizations

Read More

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7 March 2017

NYU Langone Medical Center's 2017 FACES Gala honors Loulou Foundation Co-Founders, and raises $4.7 Million To Support Epilepsy Research

NEW YORK, March 7, 2017 /PRNewswire/ -On the evening of March 6, 2017, more than 700 guests attended NYU Langone Medical Center's annual Finding A Cure for Epilepsy and Seizures (FACES) Gala, held at Pier Sixty at Manhattan's Chelsea Piers. Nearly $5 million was raised at the event to support epilepsy research and the advancement of new therapies at NYU Langone. Hosting the event was David Remnick, editor of The New Yorker, who served as the evening's emcee.

Donna Emma and Lawrence Davis chaired this year's gala in recognition of Orrin Devinsky, MD, professor of neurology, neurosurgery, and psychiatry, founder of FACES, and director of NYU Langone's Comprehensive Epilepsy Center.

NYU Langone Medical Center

2017 FACES Gala honorees Lynn and Majid Jafar with FACES founder and director of the NYU Langone Comprehensive Epilepsy Center, Dr. Orrin Devinsky. Courtesy of Josh Wong Photography.

"The FACES Gala is the world's largest fundraiser to advance epilepsy research and care," said Dr. Devinsky. "The funds raised have supported an unprecedented number of basic and clinical science collaborations that have contributed to the discovery of new epilepsy genes and new epilepsy therapies." He thanked all in attendance, noting that since 1995 FACES has supported hundreds of research initiatives that have led to important changes in the field.

Proceeds from FACES events are used to support several patient and educational programs, as well as a diverse range of research projects including new drug development, the genetics of epilepsy, sudden unexplained death in epilepsy, and many more.

Also of note was the annual live auction conducted by C. Hugh Hildesley, vice chairman at Sotheby's America. Popular prizes included a 7-night stay for 2 in Italy, tickets to the 2017 Billboard Music Awards, an exclusive 20-course, in-home dinner with famed chef Daisuke Nakazawa, and tickets to the 2017 Grammy Awards.

Majid Jafar, CEO of Crescent Petroleum, and his wife Lynn Jafar were honored for their research efforts towards finding a cure for a rare genetic disorder called CDKL5, as well as better treatments for children who have epileptic seizures and other chronic conditions. As co-founders of the Loulou Foundation, they have supported the important research of over 60 scientists at leading universities in the United States and Europe, with a total of 14 separate projects in 25 labs at 20 different institutions to date.

Special guests in attendance included Ellen Block, Susie Block Casdin, Katie and Todd Boehly, Ulrika and Joel Citron, auction co-chairs Melissa and Josh Fluhr, Loretta Glucksman, Trudy Elbaum Gottesman and Bob Gottesman, Jackie Harris, Bill Lambert, Sukey and Michael Novogratz, Colleen Olson, Kate Picco, Angela and Matt Stone, and FACES Gala underwriters Leah and Michael Weisberg.

About NYU Langone Medical Center

NYU Langone Medical Center, a world-class, patient-centered, integrated academic medical center, is one of the nation's premier centers for excellence in clinical care, biomedical research, and medical education. Located in the heart of Manhattan, NYU Langone is composed of four hospitals—Tisch Hospital, its flagship acute care facility; Rusk Rehabilitation; the Hospital for Joint Diseases, the Medical Center's dedicated inpatient orthopaedic hospital; and Hassenfeld Children's Hospital, a comprehensive pediatric hospital supporting a full array of children's health services across the Medical Center. Also part of NYU Langone is NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history, and the Laura and Isaac Perlmutter Cancer Center, a National Cancer Institute–designated cancer center. The Medical Center's tri-fold mission to serve, teach, and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education, and research. For more information, go to www.NYULangone.org, and interact with us on Facebook, Twitter, YouTube, Instagram, and Google+.

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23 February 2017

Announcement: 2017 CDKL5 Pilot Grant Programme - Request for Application

2017 CDKL5 Pilot Grant Programme (23 February 2017)

Loulou Foundation (LLF) is pleased to announce the Request for Application (RFA) for its 2017 Pilot Grant Program for CDKL5 Deficiency through its partnership with the Orphan Disease Center (ODC) at the University of Pennsylvania. Grants funded by LLF will be provided through the CDKL5 Programme of Excellence (PoE) at the ODC for one-year each and for US$150,000.00 (One hundred and fifty thousand dollars) total cost to support research as defined by the PoE priorities.

All applicants must first submit a letter of Interest (LOI) to be reviewed for consideration of a full application submission. LOIs must be received by Thursday, 9th March, 2017 at 5pm (US-Eastern Standard Time), and can be uploaded via this form, or also found on this website. Please find this link for full application guidelines including the LLF Foundation Patent Policy.

We are seeking grant applications that progress the discovery or development of treatments or cures for CDKL5 Deficiency. We recognize, however, that many gaps exist in the basic understanding of CDKL5 and its role in neurologic development. Therefore basic science projects that address these gaps are welcome as long as they are tethered to the development of a potential therapy. While the RFA is broad in scope, priority will be given to grants that cover the following areas:

  1. Development of translational biomarkers in humans and animal models of CDKL5 Deficiency.
  2. Advanced understanding of CDKL5 function or disease pathophysiology to enable therapeutic development (Suggestions: Identification of kinase substrates and CDKL5 pathways; X-inactivation and skewing in the context of CDKL5 mutations; CDKL5 pathogenesis to determine if cell-autonomous or circuit level dysfunction; determine the level of upregulation necessary to achieve therapeutic benefit).
  3. Identification of therapeutic small and large-molecules for the treatment of CDKL5 Deficiency, including: development of cellular assays for compound screening; identification of genetic modifiers.
  4. Novel therapeutic approaches for CDKL5 Deficiency, including small molecules, biologics, molecular therapies, etc.
  5. Development of animal models or reporter assays and their use in defining pathogenesis and evaluating novel therapeutics. The goal of disease model development should be to enable translational research by the investigator, as well as the broader community. For this type of proposal, please include a plan for sharing and a statement of timelines for sharing the established model.

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26 January 2017

Loulou Foundation announces the CDKL5 Forum Junior Fellowships scheme

Announcement of Junior Fellowships (26 January 2017)

As mentioned at the annual meeting of the CDKL5 Forum held earlier this month at the Wellcome Trust in London, the Loulou Foundation is pleased to announce the CDKL5 Forum Junior Fellowships scheme.

Five fellowships with an award of US$ 10,000 (ten thousand US dollars) will be granted this year to young investigators at doctoral or post-doctoral level who are active in labs working on CDKL5 Deficiency. The award funds will go to the lab of the winners and must be used to directly further the research into CDKL5 Deficiency with no deductions permitted for indirect costs, as per the policy set by the Trustees of the Loulou Foundation.

Nominations will be accepted from now until the end of 2016 from the principal investigators of the labs where the candidate is a member, in the form of a one to two page letter outlining the candidate’s eligibility based on three criteria: 1) work ethic, 2) track record of research, and 3) commitment to CDKL5 Deficiency. The fellowship awardees will be announced in January 2017.

Please send all nominations or questions by e-mail to: nominations@cdkl5forum.org

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6 July 2016

Amicus Therapeutics Expands Biologics Pipeline with New Preclinical Program for Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency Potential First-in-Class Protein Replacement Therapy for Devastating Rare Genetic Neurological Disorder with No Approved Treatments

Potential First-in-Class Protein Replacement Therapy for Devastating Rare Genetic Neurological Disorder with No Approved Treatments

CRANBURY, N.J., July 06, 2016 (GLOBE NEWSWIRE) -- Amicus Therapeutics, Inc. (Nasdaq:FOLD), a biotechnology company at the forefront of rare and orphan diseases, has expanded its biologics pipeline with a new preclinical program for cyclin-dependent kinase-like 5 (CDKL5) deficiency, a rare and devastating genetic neurological disease for which there is no currently approved treatment. Signs and symptoms typically begin with persistent, spontaneous seizures in infancy followed by severe delays in neurological development.

"The CDKL5 program fits perfectly with our vision to build a leading global biotechnology company focused on rare and devastating diseases," stated John F. Crowley, Chairman and Chief Executive Officer of Amicus. "While we remain sharply focused on the Galafold™ launch and advancing our core clinical programs in Pompe and Epidermolysis Bullosa, this CDKL5 program is an important investment in our stated strategy to expand our biologics pipeline by integrating new, innovative technologies to develop first- and best-in-class therapies for patients who are in desperate need of new treatments. CDKL5 is a rare and devastating disease with no approved treatment. Most children with CDKL5 have frequent seizures that begin shortly after birth. They experience severe impairment in neurological development, and many of them are unable to walk, talk or care for themselves. We are pleased to partner with the CDKL5 patient and medical community to elevate disease awareness as we advance towards a treatment."

Amicus has obtained the rights and related intellectual property to a preclinical CDKL5 program through the acquisition of MiaMed, Inc. Under the terms of the acquisition agreement with MiaMed, at closing, Amicus paid approximately $1.8 million in cash and approximately $4.7 million in Amicus common stock to the former shareholders of MiaMed. In addition, the former shareholders of MiaMed are eligible to receive up to $18 million upon the achievement of clinical and regulatory milestones and up to $65 million upon achievement of commercial milestones. The acquisition of MiaMed does not impact previous full-year 2016 net cash spend guidance of $135 million to $155 million.

"As the parent of a child living with CDKL5 deficiency, I strongly believe that restoration of missing CDKL5 protein holds the most promise for a future therapy," stated Michael Jasulavic, President and Chief Executive Officer of MiaMed. "It is this belief that led to the formation of MiaMed, a company dedicated to a protein replacement therapy for CDKL5. With this announcement, I am very pleased that Amicus will continue the work that was started amongst the patient and academic communities. Amicus is a truly patient-centric company with a global reach and proven R&D expertise necessary for the development of such important treatments. I am confident Amicus' advancement of this program will raise CDKL5 awareness and, most importantly, increase the potential for success in developing a CDKL5 protein replacement therapy."

"Today there is no approved treatment option for patients with CDKL5. The number of patients diagnosed has been increasing rapidly as more people learn about the disease, and physicians become more familiar with testing and diagnostic protocols. We welcome all efforts that accelerate the ongoing research and development of CDKL5 protein replacement therapy and help to raise awareness of CDKL5 deficiency," said Ashley R. Winslow, PhD, Director of Neurogenetics of the Orphan Disease Center at the University of Pennsylvania.1

"While there has been a significant collaboration between the patient organizations and academia in research and developing new treatments for CDKL5 deficiency, Amicus is among the first in the industry to add a CDKL5 development program and we look forward to learning more as the preclinical studies progress," added Dr. Winslow, who is also Chief Scientific Officer of the LouLou Foundation, a non-profit funder of CDKL5 research globally which held a beneficial interest in MiaMed.

About CDKL5 Deficiency

CDKL5 (cyclin-dependent kinase-like 5) is a gene on the X-chromosome encoding the CDKL5 protein that regulates the expression of several essential proteins for normal brain development. Genetic mutations in the CDKL5 gene result in CDKL5 protein deficiency. The disorder manifests clinically as persistent seizures starting in infancy, followed by severe impairment in neurological development. Most children affected by CDKL5 deficiency cannot walk or care for themselves and may also suffer from scoliosis, visual impairment, sensory issues, and gastrointestinal complications. CDKL5 mutations have been found in children diagnosed with cerebral palsy, infantile epilepsies, and autism, among other conditions, and the disorder was previously classified as atypical Rett Syndrome, an early seizure variant of Rett Syndrome. There are more than 1,200 documented cases of CDKL5 deficiency worldwide, with the number of identified patients increasing as genetic testing for the disorder becomes more common. For more information, and for a list of CDKL5 deficiency resources and foundations, please visit the Patient Advocacy section of the Amicus Therapeutics corporate website at http://www.amicusrx.com/patient_advocacy.php.

About Amicus Therapeutics

Amicus Therapeutics, Inc. (Nasdaq:FOLD) is a biotechnology company at the forefront of therapies for rare and orphan diseases. The Company has a robust pipeline of advanced therapies for a broad range of human genetic diseases. Amicus' lead programs in development include the small molecule pharmacological chaperone migalastat as a monotherapy for Fabry disease, SD-101 for Epidermolysis Bullosa (EB), as well as novel enzyme replacement therapy (ERT) and biologic products for Fabry disease, Pompe disease, and other rare and devastating diseases.

1Ashley Winslow, PhD, is an employee of the University of Pennsylvania and has no financial conflict of interest with MiaMed or Amicus. She does not receive any financial compensation from the LouLou Foundation although part of her salary is covered from a grant from LouLou Foundation to Penn.

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to preclinical and clinical development of our product candidates and related programs, including the preclinical CDKL5 program, the timing and reporting of results from preclinical studies and clinical trials, the prospects and timing of the potential regulatory approval of our product candidates, commercialization plans, financing plans, and the projected cash position for the Company. Words such as, but not limited to, "believe," "expect," "anticipate," "estimate," "intend," "potential," "plan," "likely," "may," "will," "would," "should" and "could," and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. The inclusion of forward-looking statements should not be regarded as a representation by us that any of our plans will be achieved. Any or all of the forward-looking statements in this press release may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding the expected benefits of the MiaMed acquisition and the anticipated impact on our business, the future prospects of the CDKL5 program, the goals, progress, timing, and outcomes of discussions with regulatory authorities, and in particular the potential goals, progress, timing, and results of preclinical studies and clinical trials, actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in our business, including, without limitation: the possibility that the expected benefits of the MiaMed acquisition may not be fully realized or may take longer to realize than expected; the possibility that we may not be able to timely and successfully develop, gain regulatory approval for or commercialize a CDKL5 protein replacement therapy; the potential that results of clinical or preclinical studies indicate that the product candidates are unsafe or ineffective; the potential that it may be difficult to enroll patients in our clinical trials; the potential that regulatory authorities, including the FDA and EMA, may not grant or may delay approval for our product candidates; the potential that we may not be successful in commercializing our product candidates if and when approved; the potential that preclinical and clinical studies could be delayed because we identify serious side effects or other safety issues; and the potential that we will need additional funding to complete all of our studies. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results. With respect to statements regarding projections of the Company's cash position, including the impact of the completion of the MiaMed acquisition on our business, actual results may differ based on market factors and the Company's ability to execute its operational and budget plans. In addition, all forward-looking statements are subject to other risks detailed in our Annual Report on Form 10-K for the year ended December 31, 2015, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2016, and our other periodic reports filed with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this news release to reflect events or circumstances after the date hereof.

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28 June 2016

LouLou Foundation Names CDKL5 Research Grant Program Awardees and appoints Chief Scientific Officer

CDKL5 deficiency causes severe neurodevelopmental impairment, seizures

28th June 2016 - London – LouLou Foundation and the Orphan Disease Center (ODC) in the Perelman School of Medicine at the University of Pennsylvania are pleased to announce the award of 11 new research grants into CDKL5 deficiency - a rare X-chromosome-linked genetic disorder that causes severe neuro-developmental impairment and early-onset, difficult-to-control seizures. This follows their announcement in February 2016 of a Program of Excellence to develop effective treatments for children with the disorder.

The grants were made following a rigorous selection process and peer review of 37 proposals received from renowned academic institutions around the world. The final awardees include leading scientific investigators at: Baylor College of Medicine, Boston Children’s Hospital, Imperial College London, Instituto Superiore di Sanità, Massachusetts General Hospital, University of California Davis Medical Center, University of Insubria, University of Massachusetts Medical School, University of Milan, and the University of Pennsylvania.

Each grant awardee will receive US$150,000 over one year to initiate novel translational research on CDKL5 deficiency, in key areas including drug screening, validating pathways, and novel therapeutic approaches. The new grants are in addition to substantial multi-year grant awards focused on the biological understanding of CDKL5’s function in the brain and development, made by Loulou Foundation in 2015 to the University of Dundee, the University of Edinburgh, and the University of Pennsylvania, which will now be joined to the Program.

Ashley R. Winslow, PhD, has also been named director of Neurogenetics for the ODC as well as Chief Scientific Officer of the Loulou Foundation. Winslow will direct the CDKL5 Program of Excellence, working with scientists and patient advocacy groups to develop a research strategy to fill key gaps in understanding CDKL5 deficiency, as well as to identify strategic partners in pharma and biotech.

“Ashley has an outstanding blend of academic credentials and industry experience that will be vital in shaping a research agenda for CDKL5 deficiency,” says Prof. James Wilson, Director of the Orphan Disease Center and Gene Therapy Program at UPenn.

The establishment of the Pilot Grant Program and the partnership between the LouLou Foundation and Penn ODC brings much-needed attention and funding for research on CDKL5 deficiency. There are currently more than 1,200 documented CDKL5 cases worldwide, with the number of identified patients increasing as genetic testing for the disorder becomes more common.

“Driven by technological advances and unprecedented data access, groups such as academia, biopharm, patient advocacy groups, and the NIH are rethinking the traditional models around translational research and clinical advancement. It is a very exciting time to be in rare disease research. I look forward to working with the scientific community to accelerate therapeutic development and biological understanding for CDKL5 deficiency,” says Ashley Winslow.

Winslow obtained her doctorate in Medical Genetics from the University of Cambridge and completed a Research Fellowship in neuro-genetics and pathology at Harvard University/ Massachusetts General Hospital. Prior to joining the ODC at Penn, Winslow was Associate Director of Neuroscience Genetics for Pfizer, World-Wide R&D, where she led efforts to integrate genomic, clinical, and biomarker datasets in order to establish data-driven approaches to target discovery and innovative clinical study design.

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28 June 2016

LouLou Foundation Names CDKL5 Research Grant Program Awardees and appoints Chief Scientific Officer

CDKL5 deficiency causes severe neurodevelopmental impairment, seizures

28th June 2016 - London – LouLou Foundation and the Orphan Disease Center (ODC) in the Perelman School of Medicine at the University of Pennsylvania are pleased to announce the award of 11 new research grants into CDKL5 deficiency - a rare X-chromosome-linked genetic disorder that causes severe neuro-developmental impairment and early-onset, difficult-to-control seizures. This follows their announcement in February 2016 of a Program of Excellence to develop effective treatments for children with the disorder.

The grants were made following a rigorous selection process and peer review of 37 proposals received from renowned academic institutions around the world. The final awardees include leading scientific investigators at: Baylor College of Medicine, Boston Children’s Hospital, Imperial College London, Instituto Superiore di Sanità, Massachusetts General Hospital, University of California Davis Medical Center, University of Insubria, University of Massachusetts Medical School, University of Milan, and the University of Pennsylvania.

Each grant awardee will receive US$150,000 over one year to initiate novel translational research on CDKL5 deficiency, in key areas including drug screening, validating pathways, and novel therapeutic approaches. The new grants are in addition to substantial multi-year grant awards focused on the biological understanding of CDKL5’s function in the brain and development, made by Loulou Foundation in 2015 to the University of Dundee, the University of Edinburgh, and the University of Pennsylvania, which will now be joined to the Program.

Ashley R. Winslow, PhD, has also been named director of Neurogenetics for the ODC as well as Chief Scientific Officer of the Loulou Foundation. Winslow will direct the CDKL5 Program of Excellence, working with scientists and patient advocacy groups to develop a research strategy to fill key gaps in understanding CDKL5 deficiency, as well as to identify strategic partners in pharma and biotech.

“Ashley has an outstanding blend of academic credentials and industry experience that will be vital in shaping a research agenda for CDKL5 deficiency,” says Prof. James Wilson, Director of the Orphan Disease Center and Gene Therapy Program at UPenn.

The establishment of the Pilot Grant Program and the partnership between the LouLou Foundation and Penn ODC brings much-needed attention and funding for research on CDKL5 deficiency. There are currently more than 1,200 documented CDKL5 cases worldwide, with the number of identified patients increasing as genetic testing for the disorder becomes more common.

“Driven by technological advances and unprecedented data access, groups such as academia, biopharm, patient advocacy groups, and the NIH are rethinking the traditional models around translational research and clinical advancement. It is a very exciting time to be in rare disease research. I look forward to working with the scientific community to accelerate therapeutic development and biological understanding for CDKL5 deficiency,” says Ashley Winslow.

Winslow obtained her doctorate in Medical Genetics from the University of Cambridge and completed a Research Fellowship in neuro-genetics and pathology at Harvard University/ Massachusetts General Hospital. Prior to joining the ODC at Penn, Winslow was Associate Director of Neuroscience Genetics for Pfizer, World-Wide R&D, where she led efforts to integrate genomic, clinical, and biomarker datasets in order to establish data-driven approaches to target discovery and innovative clinical study design.

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5 February 2016

LouLou Foundation and the University Of Pennsylvania Create Program Of Excellence for Rare Genetic Disorder that Affects Children

CDKL5 causes severe neurodevelopmental impairment, seizures

5th February 2016 - London - The LouLou Foundation and the Orphan Disease Center of the Perelman School of Medicine at the University of Pennsylvania have established a Program of Excellence to develop effective treatments for children with CDKL5, a rare X-chromosome-linked genetic disorder that causes severe neuro-developmental impairment and early-onset, difficult-to-control seizures.

There are more than 1,200 documented cases of CDKL5 worldwide, with the number of identified patients increasing as genetic testing for the disorder becomes more common. The LouLou Foundation will provide a three-year renewable umbrella grant to fully fund all aspects of the program in order to: help identify and fill gaps in basic research needed to develop medications and treatments for the disease, promote collaboration among CDKL5 investigators at leading other institutions worldwide, and engage with the biopharma industry.

The focused grant program will welcome applications from academic labs and companies around the world and will be managed by a program director to be recruited specifically for this purpose. The size of the umbrella grant will depend on the number of grant applications ultimately awarded, but the partners are confident that the resources generously committed upfront by the LouLou Foundation, in combination with Penn’s ongoing investment in orphan disease research, will make a substantial positive impact on tackling CDKL5.

“We are extremely grateful to LouLou Foundation for this grant,” said James M. Wilson, MD, PhD, director of the Orphan Disease Center and a professor of Medicine. “The marketplace provides few incentives for private-sector support of urgently needed research for orphan diseases such as CDKL5. This program will promote cooperation and synergies with other leading academic medical centers and public and private institutions, all aimed at bringing the fruits of innovative research into the clinic as rapidly as possible.”

“Penn Medicine’s Orphan Disease Center has quickly established itself as an international leader in promoting effective partnerships to make inroads against orphan diseases through its unique model to fund the best science objectively and wherever it may be,” said a spokesperson for the LouLou Foundation. “We are delighted to begin this exciting collaboration with the center on behalf of all the children and families affected by this devastating disease.”

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