Researchers from Weill Cornell Medical College led by Ronald G. Crystal, MD, the Bruce Webster professor of internal medicine and professor of genetic medicine and chairman, department of genetic medicine, published a new study (“Anti-Phospho-Tau Gene Therapy for Chronic Traumatic Encephalopathy”) in Human Gene Therapy that shows the feasibility of using gene therapy to treat the progressive neurodegenerative disorder chronic traumatic encephalopathy (CTE). The study demonstrated the effectiveness of direct delivery of gene therapy into the brain of a mouse model of CTE.

“CTE is a progressive neurodegenerative disorder caused by repetitive trauma to the central nervous system (CNS) suffered by soldiers, contact sport athletes, and civilians following accident-related trauma. CTE is a CNS tauopathy, with trauma-induced inflammation leading to accumulation of hyperphosphorylated forms of the microtubule-binding protein Tau (pTau), resulting in neurofibrillary tangles and progressive loss of neurons. At present, there are no therapies to treat CTE. We hypothesized that direct CNS administration of an adeno-associated virus (AAV) vector coding for an anti-pTau antibody would generate sufficient levels of anti-pTau in the CNS to suppress pTau accumulation thus interrupting the pathogenic process,” the investigators wrote.

“Using a serotype AAVrh.10 gene transfer vector coding for a monoclonal antibody directed against pTau, we demonstrate the feasibility of this strategy in a murine CTE model in which pTau accumulation was elicited by repeated traumatic brain injury (TBI) using a closed cortical impact procedure over five days. Direct delivery of AAVrh.10 expression vectors coding for either of the two different anti-pTau antibodies to the hippocampus of these TBI mice significantly reduced pTau levels across the CNS. Using doses that can be safely scaled to humans, the data demonstrate that CNS administration of AAVrh.10anti-pTau is effective, providing a new strategy to interrupt the CTE consequences of TBI.”

“CTE is much more prevalent than was initially realized, and there is currently no therapy available,” said the editor-in-chief of Human Gene Therapy, Terence R. Flotte, MD, Celia and Isaac Haidak professor of medical education and dean, provost, and executive deputy chancellor, University of Massachusetts Medical School. “This new work from the Crystal laboratory is potentially ground-breaking as a means to remove the offending Tau phoshoprotein.”