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Follow on Google News | Califia Bio is Developing Drugs to Treat Cognitive Effects of Multiple SclerosisCalifia Bio Inc. has been awarded a $1.7 million NIH Fast Track Phase 2 SBIR grant to develop a selective MLK3 inhibitor for the treatment of the cognitive deficits associated with Multiple Sclerosis (MS)
Although there are several new drugs which are effective at preventing relapses in multiple sclerosis, many patients continue to suffer from progressive neurologic decline. Most common symptoms involve difficulty with short term or working memory, and with planning or problem solving, often linked with difficulty self–regulating. All of these issues make holding a job and performing normal functions such as maintaining finances and health care difficult for those with moderate to severe symptoms. Neuroimaging studies suggest that these symptoms may derive from degeneration of gray matter in the brain which begins in the earliest stages of MS and progresses independently of relapses or “flare ups”. Microglia are housekeeping immune cells in the brain that keep synaptic connections between neurons healthy. In MS, microglia become activated, which leads to release of toxic and inflammatory molecules which lead to destruction of the synaptic connections between neurons. Previously, Califia Bio and collaborator Harris Gelbard M.D. showed that a non-selective MLK3 inhibitor could block the destructive effects of activated microglia in animal models of HIV associated neurocognitive disorder (HAND). This finding was published in the Journal of Medicinal Chemistry and Journal of Neuroscience. These results were extended to models of Multiple Sclerosis in Gelbard’s laboratory at the University of Rochester. “ Protein kinases like MLK3 are ubiquitous in biological signaling pathways in our bodies; the first MLK3 inhibitor we developed was very active in animal models and appeared safe in toxicology testing however it hit a very large number of “off target” kinases. Potential large pharma partners asked us to bring them a very specific MLK3 inhibitor before they were willing to risk clinical trials and we’ve got it“ said Val Goodfellow, CEO and Founder. Through NIH phase one and phase two small business innovation grants for treatment of HAND, Califia has developed a highly selective, orally active, MLK3 inhibitor, CLFB-1134, that gets into the brain. Califia has also tested the compound in animal models of Parkinson’s Disease and the positive results will be presented this Fall at the Michael J. Fox Foundation’s Parkinson's Disease Therapeutics Conference. Califia’ End
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