Scientists tip HIV drugs as cure for Alzheimers disease
News & Trends •
gene recombination was discovered as both a normal process for the brain and one that goes wrong in alzheimers disease explains dr. chun who is also a professor and the senior vice president of neuroscience drug discovery at sbp1 a recent study suggests that hiv drugs might successfully treat alzheimers disease which affects in the us alone an estimated 5.7million people1 the findings warrant immediate clinical evaluation of hiv antiretroviral therapies in people with alzheimers disease the authors of the study said1 deemed the most under-recognized public health crisis of the 21st century alzheimers disease is the 6th leading cause of death in the united states and has no known cure1 alzheimers also puts a significant strain on the american healthcare system. according to recent estimates alzheimers and other forms of dementia cost the u.s. 226 billion in 2015 and loved ones spend billions of unpaid hours caring for people with the condition. about 40 percent of these caregivers develop depression1 the medical community is hard at work trying to understand how this debilitating disorder occurs and what can be done to stop it. for instance one of the clues that researchers have so far is the so-called app gene1 the app gene encodes a protein called amyloid precursor protein found in the brain and spinal cord among other tissues and organs1 while the exact role of the app protein is still unknown scientists have found links between mutations in this gene and the risk of early-onset alzheimers disease. specifically over 50 different mutations in the app gene can trigger the condition accounting for approximately 10 percent of all early-onset alzheimers cases1 new research published in the journal nature offers unprecedented revelations into the app gene. scientists at the sanford burnham prebys medical discovery institute sbp in la jolla california found that the same type of enzyme that enables hiv to infect cells recombines the app gene in a way that creates thousands of new genetic variants in the neurons of people with alzheimers1 the findings may not only explain how app drives the toxic buildup of beta-amyloid proteins which is a hallmark of alzheimers disease but also fundamentally change how we understand the brain and alzheimers disease according to dr. jerold chun ph.d. the senior author of the new paper1 crucially the new results suggest that antiretroviral therapies that are currently used to treat hiv may be useful for treating alzheimers too1 dr. chun and his team used cutting-edge analysis techniques that focused on single- and multiple-cell samples to study the app gene in alzheimers and healthy brain samples1 they found that the app gene breeds new genetic variations within neurons through a process of genetic recombination. specifically the process requires reverse transcriptase which is the same enzyme found in hiv1 reverse transcription and reinsertion of the genetic variants back into the original genome created permanent dna changes that occurred mosaically1 according to the research published by an hiv enzyme plays a crucial role in driving alzheimers-related brain pathology by altering the app gene1 the researchers report that 100 percent of the brain samples that had the neurodegenerative condition also had a disproportionately high number of different app genetic variations compared with healthy brains1 the studys senior author explains if we imagine dna as a language that each cell uses to speak we found that in neurons just a single word may produce many thousands of new previously unrecognized words1 this is a bit like a secret code embedded within our normal language that is decoded by gene recombination dr. chun adds. the secret code is being used in healthy brains but also appears to be disrupted in alzheimers disease1 dr. chun and colleagues suggest that antiretroviral therapy that blocks the reverse transcriptase may be a successful treatment for alzheimers1 our findings provide a scientific rationale for immediate clinical evaluation of hiv antiretroviral therapies in people with alzheimers disease1 the scientists also point out that seniors with hiv who take antiretroviral medication tend not to develop alzheimers disease which may support the researchers conclusions1 the scientists also say that their findings may serve to explain a mystery that has puzzled researchers for years. the medical community widely accepts the idea that the buildup of a toxic protein called beta-amyloid causes alzheimers neuro-degeneration1 however whenever researchers tested treatments that were designed to target this toxic buildup in clinical trials such treatments failed1 but the new findings say dr. chun and team shed light on this baffling contradiction. the thousands of app gene variations in alzheimers disease provide a possible explanation for the failures of more than 400 clinical trials targeting single forms of beta-amyloid or involved enzymes chun says1 app gene recombination in alzheimers disease may be producing many other genotoxic changes as well as disease-related proteins that were therapeutically missed in prior clinical trials1 the functions of app and beta-amyloid that are central to the amyloid hypothesis can now be re-evaluated in light of our gene recombination discovery1 dr. jerold chun said jerold chun although the new findings are groundbreaking much remains to be discovered adds dr. chun. todays discovery is a step forward but there is so much that we still dont know.1 we hope to evaluate gene recombination in more brains in different parts of the brain and involving other recombined genes in alzheimers disease as well as other neurodegenerative and neurological diseases and use this knowledge to design effective therapies targeting gene recombination1