Methods and compositions for treating protein aggregation diseases

Unmet Need

Neurodegenerative disease affects more than 50 million people per year. Certain neurodegenerative diseases, like Alzheimer’s disease, result from the accumulation of amyloid-forming proteins in the brain, which results in cognitive impairment and has a substantial economic burden. Alzheimer’s disease affects over 6 million people in the United States. There is currently no effective therapy. Alzheimer’s disease is believed to be caused by the accumulation of tau proteins and Aβ plaques. In a healthy brain, AQP4 naturally clears these plaques from the brain via the glymphatic system. In the brain of an Alzheimer’s patient, however, AQP4 is dysregulated, disrupting this glymphatic clearance and resulting in the accumulation of plaques. There is a need for a therapy which restores the glymphatic clearance of Aβ plaques.

Technology

Duke inventors have developed a novel gene therapy to clear tau proteins and Aβ plaques from the brain of patients with Alzheimer’s disease. Specifically, Duke inventors have developed an adeno-associated viral (AAV) gene therapy vector containing the human aquaporin 4 (AQP4) transcript variant 1 mRNA sequence. This technology has been demonstrated with in vivo experiments in mice to increase AQP4 expression and improve clearance of tau protein and Aβ plaques.

Other Applications

This technology restores glymphatic clearance of protein aggregates, and it could also be used for the treatment of other protein-aggregation diseases such as Parkinson’s diseases, amyotrophic lateral sclerosis, dementia with Lewy bodies, frontotemporal dementia, and Huntington’s disease.

Advantages

• Can be used as a novel mechanism to eliminate the tau proteins and Aβ plaques, which accumulate in the brains of Alzheimer’s patients.
• AAV gene therapy vector can be used to deliver a single treatment for safe and durable gene therapy delivery.