When IFCR was founded, one of our primary goals was to inspire more research into CDKL5 Deficiency Disorder. As we look back on 2018, we want to share with you the amazing scientific work  your support of IFCR makes possible.

CDKL5 Centers of Excellence

IFCR has established six CDKL5 Centers of Excellence at leading health systems across the United States.  These act as points of care, as well as provide clinical research. They can be found at:

• Children’s Hospital Colorado
• Boston Children’s Hospital
• Cleveland Clinic
• St Louis Children’s Hospital
• Texas Children’s Hospital
• NYU Langone Health

At each Center of Excellence, we have arranged for a team of multi-disciplinary experts to provide care to CDKL5 patients. While IFCR does not fund patient care, our Centers of Excellence do give patients and families access to experts, all available in a single visit. This not only makes expertise available to those who would not have such access in their hometowns, it also reduces the expense and hassle of traveling for multiple provider visits. In addition to individual treatment, these experts are also working to develop standards of care for all affected patients and families.

Through our CDKL5 Centers of Excellence, we also fund clinical research to improve understanding of CDKL5 Deficiency Disorder. This disorder presents with a wide range of variability in terms of severity of epilepsy, developmental disability and other symptoms among those affected. We still lack understanding of how frequently CDKL5 mutations occur, so there may be people affected who present with only mild symptoms. Our Centers of Excellence help develop understanding in these areas.

Research to Support Families

IFCR supports Dr. Scott Demarest of Children’s Hospital Colorado in researching the parental experience of having a child diagnosed with CDKL5 Deficiency Disorder and whether that experience differs depending on age of diagnosis. He is also developing a CDKL5 Deficiency Disorder Clinical Severity Score, which will make it easier to compare data across multiple studies. Dr. Demarest hopes to clarify what the health care community does well and poorly when providing non-curable, genetic diagnoses. Similar research regarding the impact of receiving a cancer diagnosis led to radical shifts in how providers approach these challenging conversations.

National Institute of Health Natural History Study

The NIH has awarded a $29 million five-year grant to continue the Rett Syndrome Natural History Study in parallel with its sister syndromes FOXG1 Syndrome, MECP2 Duplication Syndrome and CDKL5  Deficiency Disorder.

This grant seeks to deepen understanding of core clinical features of each disorder, including whether there are any links between symptoms or outcomes and brain imaging or EEG variations. It is also exploring whether any treatments improve quality of life.

IFCR is actively supporting this research by recruiting individuals with a CDKL5 mutation. The more we know about the CDKL5 gene and the protein it generates, the more we will understand how to mitigate – and prevent – its effects.

Laboratory Science

IFCR supports specific researchers to further our understanding of the CDKL5 gene and its role and, in 2018, we have provided grants to new researchers. Dr. Jyothi Arikkath of the University of Nebraska and Dr. Scott Baraban of the University of California San Francisco are both using CRISPR-Cas technology to increase knowledge of CDKL5.

In addition to these new researchers, IFCR continues to fund Dr. Joe Zhou. He has shown that loss of CDKL5 expression disrupts multiple signal transduction pathways, impairs neural response to sensory input and creates autistic-like syndromes in mice. His lab intends to identify molecular targets for CDKL5 and explore signaling cascades. Dr. Zhou has received a multi-year NIH-funded R01 grant to expand his research.

IFCR has funded Dr. Alysson Muotri’s iPS Cell development. The Moutri lab researches neurons to drive the discovery of novel therapeutic drugs to treat or relieve symptoms of CDKL5 Deficiency Disorder.

Dr. Wenlin Liao is utilizing her funding to work towards analyzing the development of neurotransmitter systems and test a re- purposed drug for seizure suppression in three CDKL5 mouse models. In late 2017 she published a paper titled Loss of CDKL5 disrupts respiratory function in mice, offering evidence of respiratory dysfunction in CDKL5 mice.

In addition, IFCR is also excited to be funding nanobody development. Nanobodies are small, highly sensitive antibodies. Our Science Director, Heidi Grabenstatter, calls them “small but mighty.” They are extremely useful research tools and, by making them openly available to all CDKL5 investigators, IFCR will enable new research endeavors.

Pharmaceutical Studies Recruiting Patients

Two studies are currently recruiting patients with CDKL5 Deficiency Disorder, Ovid Therapeutics’ ARCADE Study and Marinus Pharmaceuticals’ Marigold Study.

The Arcade Study is a multi-site pilot study seeking to enroll a total of 15 patients with CDD.  More details can be found here.

The Marigold Study is the only placebo-controlled trial requested for registration of Ganaxolone. Once completed, Marinus should be able to file for marketing authorization. The company expects to enroll 70 to 100 patients in total. More information can be found here.

2019 and Beyond

IFCR will continue to be at the forefront of research into CDKL5. For more detail on the research supported by IFCR, please click here.