Doug Whitney should have died years ago. The 65-year-old resident of Port Orchard, Washington, has a devastating gene mutation that – according to the medical literature – causes early onset Alzheimer’s disease in everyone who inherits it.
The mutation killed Whitney’s mother and nine of her 13 siblings, and it killed Whitney’s older brother. Every one of them began showing symptoms when they were in their 40s. Most died by their mid-50s.
But Whitney has somehow escaped that fate. His memory is intact, and he has no signs of Alzheimer’s disease. Researchers want to find out why. They suspect he has another gene mutation that somehow protects him from the horrific Alzheimer’s gene mutation or that, at least, substantially delays the disease’s onset.
So Whitney has become Exhibit A in a new direction in genetics research. After years of looking for mutations that cause diseases, investigators are now searching for those that prevent them. By understanding how protective mutations work, they hope to develop drugs that mimic them and protect everyone.
The new approach is turning genetics research on its head, said Dr. Eric E. Schadt, director of the Icahn Institute, a medical research institute at Mount Sinai in New York.
In recent years, a few astounding protective gene mutations have been discovered, pretty much by accident. One prevents HIV from entering cells and another enormously reduces the amount of LDL cholesterol, the dangerous kind, that people make. Both led to drugs. The AIDS drug is a mainstay of treatment, and the cholesterol drug is in the final stages of testing.
Researchers, using systematic searches of genetic databases, also found alterations in some genes that partially protect from diseases such as heart disease, osteoporosis, Type 2 diabetes and Alzheimer’s.
But now some are starting a more ambitious project – a search for mutations that provide complete protection.
The unprecedented effort has barely begun. One attempt, being led by Schadt and Dr. Stephen H. Friend, director of Sage Bionetworks, a nonprofit research organization based in Seattle, began because the two scientists had become frustrated with the failures of drug development.
As more and more was being discovered about disease-causing genes, “I thought we should be able to develop drugs,” Friend said.
But all too often, disease-causing mutations destroy or disable genes, and drugs would have to restore what was lost, which can be difficult.
So Friend and Schadt decided to flip it around and search for a good gene mutation that counteracts the bad and – in an easier process – mimic that with a drug.
