Unmet NeedNeurodegenerative disorders are a heterogeneous group that includes Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), dementia, and Huntington’s disease. These disorders result from progressive degeneration of the structure, function, and network of neurons in the central nervous system that are unable to self-repair and regenerate, causing blindness, paralysis, and loss of various cognitive and sensory functions. Millions of people of worldwide are affected by neurodegenerative disorders, and in the United States, more than 5 million people are living with AD and at least 500,000 are living with PD. The risk for developing a neurodegenerative disorder increases with age, and is a result of a combination of both environmental and genetic factors. As overall life-span increases and the generation of aging Americans continues to grow, a greater number of people will be affected. At present, there are no cures for these disorders or ways to drastically slow disease progression. Consequently, there is a great need to develop novel approaches to treat and prevent a wide variety of neurodegenerative disorders.
Technology OverviewJohns Hopkins researchers have determined that the amyloid-beta (Ab) and alpha-synuclein aggregates that arise in the neurons of those with AD and PD and promote A1 astrocyte formation and the release of neurotoxic cytokines also significantly induce the activity of a serine/threonine-protein kinase. When this kinase was inhibited by various small molecules neuroinflammation was reduced, Ab and alpha-synuclein aggregate activation and A1 astrocyte formation was blocked, and neurons were secured. In a PD mouse model with alpha-synuclein preformed fibrils (PFFs), a known RIPK2 inhibitor significantly rescued PFFs induced pathologies.
Stage of DevelopmentThe inventors have identified a novel, potential therapeutic target for neurodegenerative disorders including AD and PD. Further research and development are required to generate a first in class, orally active targeted kinase inhibitor with disease modifying effects for various neurodegenerative pathologies in actual human patients.
