Non-invasive One-Time Treatment for Familial Alzheimer’s Disease Shown to be Effective in Mice

Non-invasive One-Time Treatment for Familial Alzheimer’s Disease Shown to be Effective in Mice

A new potential treatment for Alzheimer’s disease has been developed by an international team of researchers that has been shown to be effective in mouse models of the disease.

The research study, led by the Hong Kong University of Science and Technology (HKUST), uses brain-wide genome editing technology and has been shown to reduce AD pathologies in mice. The treatment has tremendous potential for treating familial Alzheimer’s Disease (FAD) – a congenital form of Alzheimer’s disease. While tests can be conducted to determine whether individuals will develop FAD before symptoms of the disease appear, there is no cure for FAD.

Genome-wide editing is the natural option for curing FAD, but there have been several challenges to overcome. One of the biggest issues is how to get a genome-editing tool where it is needed in a non-invasive procedure. Second, while there are genome-editing technologies that could potentially be used, studies have failed to demonstrate beneficial outcomes, as the technologies are not effective at editing the genome throughout the brain.

Those problems have now been solved. The researchers developed a novel genome-editing system that is able to cross the brain-blood barrier and can deliver an optimized genome editing tool to the entire brain. The study showed the tool achieves efficient genome editing across the entire brain, with the treatment provided using a one-time intravenous injection. That one-time treatment could see the effects last a lifetime.

The researchers say their genome-editing tool disrupted FAD-inflicted mutations in mouse models of the disease and ameliorates AD pathologies throughout the entire brain. Amyloid levels remained low for 6 months post-treatment, which is around 1/3 of the normal lifespan of the mice. None of the mice experienced any detectable side effects from the treatment.

“As the first demonstration of efficient brain-wide genome editing to alleviate Alzheimer’s disease pathology throughout the whole brain, this is really an exciting development,” said Prof. Ip, Morningside Professor of Life Science and Director of the State Key Laboratory of Molecular Neuroscience at HKUST. “Our work is an important milestone for the use of genome editing in treating hereditary brain diseases and contributes to the development of precision medicine for inherited forms of neurodegenerative diseases.”

You can read more about the study in the paper – Brain-wide Cas9-mediated cleavage of a gene causing familial Alzheimer’s disease alleviates amyloid-related pathologies in mice– which was recently published in Nature Biomedical Engineering. DOI: 10.1038/s41551-021-00759-0