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Novel Virus-Like Particle (VLP)-Based Vaccines Against Alzheimer's Disease Tau Pathology

技术优势

Highly efficient, safe, economical, andstate-of-the-art immunotherapy approach based on a Virus-Like Particle (VLP)platformTargets four disease-related modifications inmicrotubule associated tau protein (MAPT)This VLP-based immunotherapy, targeting p-MAPT,provides a potential opportunity for developing future therapies against p-MAPT/NFT-inducedneurodegenerative alterationsElicits antibodies against pathological tauwithout inducing a severe inflammatory responseVaccination leads to significant improvements inrecognition and spatial memoryVaccination decreases neurofibrillary tangles inthe hippocampus and cortex in a mouse model of tauopathyPrevents neuronal cell loss induced by taupathologyApplicable to neurodegenerative tauopathies (suchas Alzheimer’s Disease) and tauopathy-resultant from TBI and CTE

详细技术说明

Aunique virus-like particle (VPL)-based platform technology to develop vaccinesagainst tauopathies.

*Abstract

Thisimmunotherapy approach has significant potential as a therapy forneurodegenerative tauopathies such as, for example, Alzheimer’s disease andMAPT pathology induced by traumatic brain injury.

*Background

Alzheimer’s disease (AD) is a neurodegenerativedisease characterized by progressive decline in cognition. The majorpathological hallmark responsible for this decline is the accumulation ofhyperphosphorylated Microtubule Associated Protein Tau (MAPT or Tau) intoaggregated neurofibrillary tangles (NFTs). This pathological misfolding of MAPTis also responsible for several other neurodegenerative tauopathies besides AD andfollowing traumatic brain injuries (TBIs). Although pathological-MAPT (p-MAPT) hasbeen therapeutically targeted to halt MAPT-mediated neurodegenerative cascades,many such approaches are not feasible in humans or did not meet successfulend-point when tested in devastating movement disorders with pure tauopathy. Furthermore,despite mounting evidence that pathological misfolding in MAPT ensue inresponse to TBI/chronic traumatic encephalopathy (CTE), no attempts have beenmade to target p-MAPT to improve the clinical outcome following TBI. Based onthis, there is an urgent need to develop highly efficacious MAPT-targetedtherapies to block neurodegenerative changes in AD and related tauopathies aswell as following TBI/CTE.One promising therapeutic strategy currently beingtested in AD is immunotherapy. There are several challenges with this approach.First, it is often difficult to elicit strong antibody responses againstself-antigens like MAPT. Second, immune responses against self-antigens havethe potential to cause substantial side effects. Furthermore, while theadministration of purified MAPT antibodies (passive immunization) showspromising trends in reducing pathological MAPT in recent studies, they are notcost-effective due to the prohibitively expensive process of making purifiedantibodies. Finally, in the context of MAPT pathology, neuroinflammation, whichcan ensue in response to brain trauma, accelerates MAPT pathology and cognitiveimpairment in an hTau mouse model of tauopathy (Bhaskar et al., 2010, Neuron68:19-31). It is therefore important to develop a MAPT-targeted immunotherapythat can successfully elicit a targeted immune response against NFTs whilelimiting the inflammatory consequences.

国家/地区

美国