The goal of this invention is to overcome the challenges of previous approaches by selectively targeting treatments to the CNS without peripheral toxicity. Kinase inhibition is targeted to the central nervous system (CNS) by combining brain-permeable kinase inhibitors and a brain-impermeable blocking molecule.
Worldwide, there are over 10 million people affected by Parkinson’s disease, epilepsy and glioblastoma and, as the worldwide population ages, the incidence of these diseases is expected to rise. While many promising approaches have been tested to treat brain disease, most have failed because of insufficient blood-brain barrier permeability and/or excessive peripheral toxicity. The novel approach to treating brain disease described in this technology combines newly developed, more potent kinase inhibitors with novel blocking compounds. This combination targets kinase inhibitor treatment to the CNS. This novel invention provides the following advantages: 1) Targets kinase inhibitors (disclosed in SF2019-123) to the CNS when combined with novel blocking compounds. 2) This method can be used to treat a broad range of diseases of the brain including Parkinson’s and glioblastoma. 3) These compounds are expected to have decreased systemic toxicity and improved target specificity when combined with novel blockers.
Medicinal chemists at the University of California, San Francisco have generated a novel class of blocking compounds that saturate a specific factor that is naturally occurring in the periphery. In turn, this drives newly developed kinases to the CNS with the goal of increasing the blood-brain permeability of the kinases while decreasing negative off-target effects.
Treatment of CNS diseases such as epilepsy, alcohol use disorder, and growth suppression associated with chronic mTOR inhibition. Treatment of brain cancers such as glioblastoma and tuberous sclerosis.
To develop and commercialize the novel blockers, chimeric kinases and method of use to treat diseases including Parkinson’s, epilepsy, and glioblastoma.