Program of Excellence for Rare Genetic Disorder Affecting Kids

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, the London-based LouLou Foundation and the Orphan Disease Center of the Perelman School of Medicine at the University of Pennsylvania have established a Program of Excellence.

There are more than 1,200 documented cases 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 marketplace provides few incentives for private-sector support of urgently needed research for orphan diseases such as CDKL5, a rare X-chromosome-linked genetic disorder.’

The program will launch a new focused grant program welcoming 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."

CDKL5 stands for cyclin-dependent kinase-like 5, a protein whose gene is located on the X chromosome, one of the sex chromosomes. The CDKL5 gene provides instructions for making a protein that is essential in forming the connections for normal brain development, with mutations causing a deficiency in the protein level.

Most children affected by CDKL5 (about 90 percent of whom are girls) suffer from seizures that begin in the first few months of life. Most cannot walk, talk, or feed themselves, and many are confined to wheelchairs, dependent on others for everything. Many also suffer with scoliosis (curvature of the spine), visual impairment, sensory problems, and gastrointestinal difficulties.

CDKL5 mutations have been found in children diagnosed with cerebral palsy and autism, among other conditions, and the disorder was previously classified as an early seizure variant of Rett Syndrome. Mutations in the gene are usually spontaneous occurrences, rather than inherited, and physicians do not yet know the full range of CDKL5 disorders.

"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." Loulou Foundation was founded in 2015 as a private non-profit UK foundation for the purposes of advancing research into the understanding and development of therapeutics for CDKL5 and other neurodevelopmental disorders. The Foundation has already made substantial grant commitments and investments in the United States and Europe.

Penn Medicine''s interdisciplinary Orphan Disease Center, established in 2011 with a $10 million gift, provides core laboratories and tailored technical support and expertise to eradicate orphan diseases, while also supporting approaches and technology platforms to treatments that are common among various orphan diseases. Cooperating with other academic institutions, the National Institutes of Health, the pharmaceutical industry, and philanthropic organizations, the center aims to reduce the technological and financial burdens on investigators working in isolation by supporting a wide array of collaborative approaches.

Source: Newswise