Lafora disease (LD) is a rare, progressive, autosomal recessive neurodegenerative disorder characterized by intractable seizures, inexorable neurological deterioration, cognitive decline, dementia, and death within 10 years of onset. It is caused by loss-of-function mutations in either the laforin gene (EPM2A) or malin gene (NHLRC1) and is associated with gradual accumulation of Lafora bodies, aggregates of poorly branched, hyperphosphorylated, insoluble glycogen also known as polyglusan. LD usually begins in late childhood or adolescence. Animal studies have shown that reducing the production of glycogen in neurons can prevent the disorder. Valerion’s goal is to enzymatically degrade neuronal glycogen, preventing its aggregation and rescuing the neurons from degeneration.
In preclinical proof-of-concept studies, Valerion and collaborators at the University of Kentucky demonstrated in vitro and in vivo, the ability to deliver VAL-0417 to the skeletal muscle and brain with retention of up to 24 hours following intracerebroventricular (ICV) injection in Lafora mouse models. These early but encouraging data demonstrate preclinical proof-of-concept for VAL-0417 and further validate the Valerion platform technology for use in CNS disease.