New compounds identified through high throughput screening which improve mitochondrial function of Friedreich ataxia cells.
Friedreich ataxia (FA) is an autosomal recessive, inherited neuro- and cardio-degenerative disorder characterized by progressive ataxia of all four limbs, skeletal deformities, and hypertrophic cardiomyopathy. FA is the most prevalent inherited ataxia, affecting about 1 in 50,000 people in the United States. Most patients are confined to a wheelchair by their late 20s with myocardial failure and/or arrhythmias being the most common cause of premature death. FA is caused by mitochondrial dysfunction secondary to decreased expression of the protein Frataxin.
Currently, there are no approved drugs to treat FA and the resultant disability, prolong the life of a FA patient, or cure the disorder.
Dr. Wilson and his team at Penn developed a novel in vitro high throughput screening (HTS) platform for screening drug candidates for treatment of FA. Using such systems, the team has screened 342,000 compounds and identified lead candidate compounds that increase the expression of Frataxin protein and support the survival of primary FA fibroblasts. These compounds adhere to Lipinski rules, are highly specific to FA, and are active in the low nanomolar range. Several optimized modifications of the lead compounds have been generated.
- Regulatory fast-track: FA is a FDA designated orphan disease with no approved treatment
- Access to the expertise and resources of Wilson’s lab
Robert Wilson M.D., Ph.D. is a world-renowned expert studying Friedreich ataxia for over 18 years, both in clinical and lab research settings. Dr. Wilson is co-Director of the CHOP- Penn Center of Excellence for Friedreich’s Ataxia Research which involves 13 centers in 5 countries. The Center sees more FA patients than any other center in the world and is actively developing biomarkers, clinical protocols, and ataxia scales for use as Phase III endpoints.
Dr. Wilson was the Scientific Director of Friedreich’s Ataxia Research Alliance for 7 years, and currently serves on the Medical Research Advisory Board for the National Ataxia Foundation. The Wilson Lab has developed, and/or utilizes, most of the models of the disorder, has the reagents and expertise to measure all aspects of FA biochemistry, and is actively collaborating with FA researchers throughout the world.
Stage of Development:
- Lead candidates identified and validated in in vitro models
- Lead optimization is underway
Issued US patent (4/17/2015) 9,000,009 and pending Divisional application
Cotticelli, G.M., et.al., 2011. J. Biomol Screen. 17(3). 303-13.
- Sponsored research
Docket # V5006