Medicine and Health Sciences Commons^™

Defining Patient Cohorts For Guiding Clinical Trials And Treatment In Lafora Disease: A Model For The Rare Disease Community, Katherine Janae Donohue

Theses and Dissertations--Molecular and Cellular Biochemistry

In the US, approximately 8000 rare diseases have been identified. Combined, rare diseases impact more than 30 million people in the U.S. alone, with 75% of those being children. However, research, funding, and therapeutic development for the rare disease community remains challenging because of the incredible diversity – not only between diseases, but often even within a single disease.

LD is an ultra-rare childhood dementia and epilepsy caused by mutations in one of two driver genes: EPM2A, which encodes for the glycogen phosphatase laforin, and EPM2B/NHLRC1, which encodes the E3 ubiquitin ligase malin. Children with LD …

Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood

Theses and Dissertations--Molecular and Cellular Biochemistry

Lafora disease (LD) is a rare yet invariably fatal form of epilepsy characterized by progressive degeneration of the central nervous and motor systems and accumulation of insoluble glucans within cells. LD results from mutation of either the phosphatase laforin, an enzyme that dephosphorylates cellular glycogen, or the E3 ubiquitin ligase malin, the binding partner of laforin. Currently, there are no therapeutic options for LD, or reported methods by which the specific activity of glucan phosphatases such as laforin can be easily measured. To facilitate our translational studies, we developed an assay with which the glucan phosphatase activity of laforin as …