Gladstone: Part of the Univ of Ca, San Fran
AD partnership with MRK; and several other activities.
gladstone.ucsf.edu
Mentioned in WSJ Column:
IN 1993, Allen Roses at Duke University discovered that a gene called apoE4 increases the risk of Alzheimer's. About all he got for his trouble was loss of funding and skepticism -- even though apoE4 turns out to be behind 50% to 70% of Alzheimer's cases. (If you inherited two copies of apoE4, one from mom's egg and one from dad's sperm, your risk of developing AD is 50% to 90%; with zero copies, the risk is 20%.)
ApoE4 research hung on by its fingernails, and this month drug giant Merck and Gladstone announced a research collaboration, with a $3.25 million up-front payment, to develop Alzheimer's therapies based on apoE4.
One approach Gladstone scientists are working on is to turn the protein that apoE4 makes into its healthy cousin, apoE3. "We've identified a dozen molecules that do this," says Dr. Mahley. Another is to block an enzyme that snips the apoE4 protein into fragments. These snippets enter neurons, attack their vital energy-making mitochondria, form toxic tangles and thus kill them. If you prevent the snippets from forming, maybe neurons would never face these killers.
In a recent paper, Dr. Roses, now at GlaxoSmithKline, expressed guarded optimism about a molecule called rosiglitazone. In a Phase II trial of 511 patients, it produced "significant clinical improvement" in some patients, GSK reported in January. Rosi seems to increase the number of mitochondria in neurons. Since fragments of the apoE4 protein attack mitochondria, a drug that keeps making new ones would keep neurons alive despite the attacks, like a battalion that remains at full strength, despite casualties, with new recruits.
Anti-inflammatory drugs and statins may protect brain neurons from Alzheimer's. So might blocking an enzyme that changes harmless proteins into the toxic tangles that kill neurons, or compounds that increase synapses as fast as Alzheimer's destroys them, or ...
Whole WSJ column: online.wsj.com |
