The BACE1 gene drives the production of amyloid-beta proteins in the brain, and is commonly associated with Alzheimer’s disease. These proteins accumulate and form amyloid plaque – one of the key features of the pathology of Alzheimer’s disease.
Last year, research published in Nature Neuroscience successfully edited out the BACE1 gene in the brains of adult mice, using CRISPR-Cas9 gene editing. CRISPR is a technology that can be used to target and cleave specific DNA sequences, allowing new DNA to be inserted or removed. Within 8-12 weeks of treatment, mice displayed improved cognitive function and reduced amyloid plaque buildup.
Drugs targeting BACE1 are currently undergoing clinical trials, however editing out the BACE1 gene entirely would have the advantage of being permanent.
Significantly, the study found no evidence of off target mutations, though the authors still advised caution in this regard, as gene editing cannot be undone. Furthermore, it is important to remember that normal mice do not develop Alzheimer’s disease.. To produce the mouse models used in this study, genetic alterations were made to accelerate amyloid plaque formation, for example by knocking in the gene for amyloid precursor protein. BACE1 might therefore have played a larger role in these disease models than in real human disease.
In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease: https://doi.org/10.1038/s41593-019-0352-0