A study of a rare gene mutation that protects people against Alzheimers provides the strongest evidence yet that excessive levels of a normal brain substance,beta amyloid,are a driving force in the disease – bolstering hopes that anti-amyloid drugs already under development might alter the diseases course or even prevent it.
So far,the drugs have not succeeded a drug that failed spectacularly in 2010,semagacestat,actually made people with Alzheimers worse and gave rise to soul-searching in the field but scientists not connected with the new study said it suggested drug companies big bets on anti-amyloid treatments could yet pay off.
The implication for drug development is hugely important, said David Altshuler,a genomics expert at Harvard Medical School.
And Samuel Gandy,an Alzheimers researcher who directs the Mount Sinai Center for Cognitive Health,called the finding the most significant in the field in two decades,since researchers first reported a mutation that leads to the disease.
The protective mutation,whose discovery was reported online Wednesday in the journal Nature,is highly uncommon it is not the reason most people do not develop Alzheimers. But what intrigues researchers is how it protects the brain.
Mutations that cause Alzheimers lead to excessive amounts of beta amyloid in the brain; by contrast,the protective mutation slows beta amyloid production,so people make much less.
This paper provides strong evidence that it would work in the general population if you did it right, Altshuler said.
Scientists at the drug companies agreed. We are thrilled, said Ryan Watts,one of the authors of the new paper and head of the neurodegeneration labs at Genentech,which is developing two drugs to reduce brain amyloid levels.
Richard Mohs,leader of neuroscience early clinical development at Eli Lilly,said the firm was very encouraged by these study results.
Many questions remain,of course. Most people do not have the protective gene mutation,but as common as Alzheimers is,most people do not get it. It is not clear why. And most who develop Alzheimers do not have one of the rare gene mutations that cause it. The reasons for their disease are unclear.
The investigators,led by Kari Stefansson,chief executive at DeCode Genetics,an Icelandic company,looked at genomes of North Americans and found the gene mutation in only about 1 in 10,000 people. That indicates,Stefansson said,that the mutation arose relatively recently in Scandinavia.
There is as yet no way to prevent Alzheimers and,outside of families with one of the rare disease-causing mutations,no way to know who is going to get it.