This drug failed to treat cancer, but it could improve dementia

Log in with your Medical News Today account to create or edit your custom homepage, catch-up on your opinions notifications and set your newsletter preferences.Sign up for a free Medical News Today account to customize your medical and health news experiences.Dr. Kenneth Kosik, the Harriman Professor of Neuroscience at the University of California (UC), Santa Barbara recently led a team of experts who were focusing on using a known drug to treat the toxic buildup of a protein called "tau" in the brain.Usually, tau proteins play a role in stabilizing microtubules. Then, in the laboratory, the scientists converted these sampled cells into stem cells and then into neurons so that they could trace what kinds of genetic mutation might affect tau.The findings, which the researchers report in the journal Science Translational Medicine, indicated that three genes presented dysregulations in tau mutations.Of these three genes, however, the team focused on one — RASD2 — which drives the activity of energy-producing molecules called GTPases."People had already talked about this gene as possibly involved in Huntington's disease, which is another neurodegenerative disease," explains Dr. Kosik, adding that RASD2 and another similar gene called RAS have attracted a lot of attention from researchers because they appear to be responsive to drugs."There are drugs or potential drugs or small molecules that are out there that could affect the levels of this gene," Dr. Kosik notes.While studying RASD2, the researchers were intrigued by a GTPase called RHES, which this gene encodes. It seems to have a selective effect on only the forms of tau that are predisposed to forming the neurofibrillary tangles," Dr. Kosik observes.To ensure that Lonafarnib acted by attacking farnesylated RHES, the researchers looked at another set of mouse models of dementia in which they activated a gene that blocks RHES production.In this case, the behavior of the mice improved in the same way as it had with Lonafarnib treatment, which proves that the drug's action on farnesylated RHES is responsible for its benefits."This makes us begin to think that although indeed the drug is a general farnesyl transferase inhibitor, one way it's actually working is by specifically targeting the farnesylation of RHES.