Gene Therapy for Idiopathic Parkinson's Disease

There is no cure or disease-modifying therapy for patients diagnosed with idiopathic Parkinson’s Disease (idPD) that carry no genetic mutations and have no family history of this devastating neurodegenerative condition. Mark Therapeutics (MarkTx) is addressing the unmet needs of idPD patients by developing a first-in-class disease-modifying gene therapy that can halt disease progression in this largest group of Parkinson’s patients (~80% of all cases). MarkTx’s solution is to use an Adeno-Associated Viral (AAV) gene therapy tailored specifically to idPD patients, which will compensate for the epigenetic loss of expression of a specific protein in these patients, restore critical cellular functions in dopaminergic (DA) neurons and halt their pathological loss. Using our first experimental candidate (Mark101), we obtained proof-of-concept for efficacy and safety of MarkTx’s gene therapy and demonstrated that one-time AAV-driven expression of functional PLA2g6L protein can stop pathological loss of DA neurons in substantia nigra, and significantly slow progression of motor dysfunction in preclinical idPD-like aging mouse model. Intellectual property of MarkTx is secured by 4 issued patents and an exclusive license from Boston University. MarkTx is seeking SBIR Phase I financing to perform feasibility studies and rigorous preclinical optimization /validation of the improved candidates for Mark’s therapy. The specific Aims of Phase I are: Aim 1: Optimization and initial testing of new (improved) AAV candidate constructs. Aim 2: In vitro validation of therapeutic potential of best candidates in human DA neurons. Aim 3: In vivo treatment optimization and validation of PLA2g6L delivery to DA neurons in live animals. MarkTx’s team has strong scientific and business experience and is fully qualified to achieve all the goals of the current proposal. Successful completion of Phase I will identify the best therapeutic candidate(s) for MarkTx’s gene therapy, validate their ability to express PLA2g6L and restore critical cellular function in DA neurons that is being lost in idPD patients. Achievement of well-defined milestones will further de-risk MarkTx therapy and ensure effective transition to SBIR Phase II. NINDS/SBIR funding is essential for development and eventual commercialization of MarkTx’s highly promising, first-in-class disease-modifying gene therapy tailored specifically for idPD patients. We strongly believe our innovative therapeutic approach to idPD will be a game- changer and a major step towards ultimate victory in the fight against this currently incurable and devastating disease in aging humans. The goals of MarkTx’s proposal fully align with the mission of the NINDS.