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Project

AAV9-based delivery of an anti-BACE1 nanobody to treat Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia whose progression eventually leads to death. The cause of the disease is still not well understood. Current evidence suggests that the presence of amyloid plaques composed of amyloid beta peptide (Abeta) in the brain is central to disease pathology, playing a role in neuronal toxicity and subsequent cognitive decline. Abeta is generated by sequential cleavage of neuronal amyloid precursor protein (APP) by beta and gamma secretases. Recently, the beta secretase BACE1 has emerged as the target of choice to try to reduce amyloid plaque deposition in the brain and ameliorate subsequent neurological decline. One of the most promising approaches makes use of nanobodies specific to BACE1 to decrease its activity in the brain. However, immunobased therapies have been challenging due to the need for repeated injections and poor bioavailability due to difficulties in crossing the blood brain barrier. It has recently been shown that adeno-associated viral vectors (AAV) designed for gene therapy can successfully target various structures of the brain when administered intravenously or into the cerebrospinal fluid. Therefore, we propose to develop and validate an AAV vector system encoding a nanobody targeting BACE1 to improve AD pathology. The AAV9 vector will have the advantage of providing long-term production of the nanobody at clinically relevant levels throughout the brain after a single injection.

Date:1 Oct 2016 →  30 Sep 2019
Keywords:anti-BACE1 nanobody, AAV9, Alzheimer’s Disease
Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing