Rare gene mutation protects against Alzheimer's

While combing through the DNA of 1,795 Icelanders, scientists identified a rare gene mutation that appears to protect people from getting Alzheimer's by slowing production of beta amyloid in the brain. Details are published in the journal Nature, and publications from The New York Times to Bio-IT World have written pretty detailed stories looking at the discovery and its implications for drug discovery.

"This variant confers a very large protection against Alzheimer's disease," lead researcher Kari Stefansson, CEO of DeCode Genetics, told Bio-IT World. The Reykjavik, Iceland, company offers disease risk-assessment DNA-based diagnostic tests, plus personal genome scans.

The protective variation is known as A673T, and occurs at a rate of about 0.5% in Scandinavian populations--a rare variation of the amyloid precursor protein gene. Folks such as Eli Lilly's ($LLY) Dr. Richard Mohs, who leads neuroscience early clinical development for the company, told The New York Times that the finding reaffirms his drug company's strategy of focusing on drugs to reduce beta amyloid levels, despite industry setbacks. Similarly, Ryan Watts, head of neurodegeneration labs at Genentech and an author of the paper, said in the NYT article that the results left researchers "thrilled." As the NYT story notes, Genentech is developing two drugs focused on reducing amyloid levels in the brain.

Stefansson told Bio-IT World that the finding validates the development of BACE1 inhibitors to combat Alzheimer's. That's because the A673T mutation sits near a site targeted by the enzyme beta secretase, or BACE1, which contributes to amyloid protein formation--thought to be a primary factor in Alzheimer's development. Merck ($MRK) and Genentech are developing drugs with this particular target.

"It protects against age-related cognitive decline in the elderly who do not have Alzheimer's," Stefansson told Bio-IT World. "The implication there is that if Big Pharma finally develops an effective inhibitor of beta secretase, it should not only be given to those at high risk of Alzheimer's disease, it should probably be put into the drinking water!"

The finding is early-stage and years from tangible drug development work, but Stefansson said the research will continue in an effort to learn more about the A673T mutation.

- read the NYT article (sub. req.)
- check out the Bio-IT World piece
- here's the Nature abstract