Genetic therapies for Alzheimer’s disease: a scoping review
| Autor: | Matthew J Lennon, Vanessa Raymont, Grant Rigney, Perminder S. Sachdev |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Apolipoprotein E2
Tau protein Apolipoprotein E4 tau Proteins Disease Bioinformatics Mice Downregulation and upregulation Neurotrophic factors Alzheimer Disease Nerve Growth Factor Medicine Dementia Animals Humans Vector (molecular biology) Amyloid beta-Peptides biology business.industry General Neuroscience Brain-Derived Neurotrophic Factor General Medicine Genetic Therapy medicine.disease Clinical trial Psychiatry and Mental health Clinical Psychology Nerve growth factor biology.protein Geriatrics and Gerontology business |
| Popis: | Effective, disease modifying therapies for Alzheimer’s disease (AD) remain a quandary, following a panoply of expensive failures in human clinical trials. Given the stagnation in therapeutics, alternative approaches are needed. Recent successes of genetic therapies in other neurodegenerative diseases may highlight the way forward. This scoping review explores suggested targets of genetic therapy in AD, with a focus on vector-based approaches in pre-clinical and clinical trials. Putative targets of genetic therapies tested in pre-clinical trials include amyloid pathway intermediates and enzymes modulation, tau protein downregulation, APOE4 downregulation and APOE2 upregulation, neurotrophin expression (nerve growth factor (NGF) and brain-derived neurotrophic factor), and inflammatory cytokine alteration, among several other approaches. There have been three completed human clinical trials for genetic therapy in AD patients, all of which upregulated NGF in AD patients, showing some mixed evidence of benefit. Several impediments remain to be surpassed before genetic therapies can be successfully applied to AD, including the challenge of delivering monogenic genetic therapies for complex polygenic disorders, risks in the dominant delivery method (intracranial injection), stability of genetic therapies in vivo, poor translatability of pre-clinical AD models, and the expense of genetic therapy production. Genetic therapies represent an exciting opportunity within the world of AD therapeutics, but clinical applications likely remain a long term, rather than short term, possibility. |
| Databáze: | OpenAIRE |
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