Genetic Therapies for Alzheimer's Disease: A Scoping Review.
Level 5 - mechanism / opinion, no new human data
Scoping review summarizing preclinical mechanism studies and three early-phase human trials
PubMed 34569966 · doi:10.3233/JAD-215145
What was done
This scoping review examined suggested targets and vector-based approaches for genetic therapy in Alzheimer's disease (AD) across preclinical models and human clinical trials.
What was found
Preclinical studies have investigated targets including amyloid pathway intermediates and enzyme modulation, tau downregulation, APOE4 downregulation and APOE2 upregulation, neurotrophin expression (nerve growth factor [NGF] and brain-derived neurotrophic factor), and inflammatory cytokine modulation. Only three human clinical trials of genetic therapy for AD have been completed, all focused on upregulating NGF, showing mixed evidence of clinical benefit. The abstract reports no numerical outcome data, sample sizes, or statistical results.
Why it matters
As traditional small-molecule and antibody approaches for AD face challenges, genetic therapies offer alternative strategies targeting disease-modifying mechanisms, though clinical application remains a distant goal.
Limits
The abstract does not provide quantitative data, patient numbers, or detailed outcomes for the three completed human trials. Key translational hurdles identified include the difficulty of treating a complex polygenic disorder with monogenic therapies, procedural risks associated with intracranial delivery, vector stability in vivo, poor translation from animal models, and high production costs.
Cited by
- supports Neurodegenerative diseases, including Alzheimer's disease, are rarely caused by a single mutation in a single gene; the vast majority of cases are caused by a combination of many hundreds or thousands of genetic risk factors interacting with environmental and lifestyle exposures.