The CDKL5 genetic disorder was first described in 2004, and initial research studies began shortly thereafter. Early research efforts have focused on small case series reports of individuals affected by CDKL5, as well as a few attempts to characterize the CDKL5 protein and it’s interaction with other proteins in the brain, particularly the MECP2 protein in Rett Syndrome.
Several small case series reports have attempted to describe the physical characteristics of the disorder, and establish diagnostic criteria, however, these are based on a small number of patients, and conclusions are difficult to interpret.
Research on CDKL5 is in its infancy, in terms of the quantity of research projects, and the amount of money available for such research. Yet CDKL5 remains an exciting research challenge in the scientific community, and there is renewed interest in pursuing this genetic puzzle, especially as it relates to Rett Syndrome, infantile spasms and autism.
Our foundation aims to be at the forefront of CDKL5 research, and in collaboration with leading scientists, we are on the threshold.
2013 research goals include, but are not limited to, the following:
Continue testing existing compounds via high through-put screening in iPS cells to identify possible neurologic modifiers that can then be taken into animal trials and clinical development. In a relatively short period of time, our goal is to test hundreds of compounds/molecules already developed to see if any of them have a positive effect on the function of CDKL5 neurons. This is an important but costly endeavor in CDKL5 research, and could help us identify treatment options for some of the serious symptoms that affect people living with CDKL5, such as seizures and gastrointestinal difficulties.
Fund clinical projects that study seizures, bone health, the gastrointestinal system and other organ systems that impact people living with CDKL5. While we are working aggressively to understand the CDKL5 protein and all its function in the brain and body, we hope to identify practical and readily accessible therapies that will help improve the physical health and quality of life of our children now.
Establish a clinical consortium of CDKL5 Centers of Excellence in the United States, and work with our partner organizations to establish CDKL5 centers internationally. These Centers of Excellence are an important aspect of understanding the spectrum and course of CDKL5 disorder, and fostering excellence in medical care for our families by developing standards of care, evidence based medicine and guidelines for diagnosis and therapeutic approaches. These CDKL5 Centers of Excellence will also be key sources for clinical trials. IFCR's goal is to have at least three centers established in the U.S by the end of 2013.
Continue supporting the comprehensive international CDKL5 database that was begun in 2012, and work with Rett Syndrome in joining the NIH sponsored clinical consortium for a CDKL5 natural history study beginning in 2014. A natural history study will give us a more complete picture of CDKL5 throughout a persons lifespan, and will help us identify interventions that improve the quality of life for our families, such as types of physical and speech therapies, augmentative communication, dietary changes, support services, etc.
Start a repository for biological samples from patients with CDKL5. Developing a comprehensive tissue bank can take several years. This process needs to be started as soon as possible so that tissue samples are available to scientists as the research pace accelerates.
Continued funding for ongoing studies that are attempting to identify function and targets of the CDKL5 protein. This type of laboratory research is fundamental to our understanding of how and where the CDKL5 protein works in the human brain and body. The knowledge obtained from these studies will help direct clinical and laboratory research for years to come.
Explore the techniques of gene therapy, stem cell therapy and protein replacement therapy. IFCR is exploring the feasability, safety and ethics of these techniques. One of the first steps in the process is to show proof of concept in cell and animal models, and then to develop a delivery system into the brain for human use. It is important to understand that these types of projects, from beginning to end, including clinical trials will take many years and likely cost over $10 million. Success with these techniques in most disorders and diseases has not been proven, but as science advances, we are optimistic that CDKL5 could benefit from these techniques in the future.