Your brain cells are dying. So are mine. Nerve cells in our brains die off throughout our lifetime, from youth to old age, and usually it doesn't make much difference at all in our daily lives. But when brain cells begin to die off prematurely and en masse, the result can be diseases like Alzheimer's and Parkinson's, or the less-dramatic but often equally tragic senile dementia.
Scientists now are working to understand how cells tell themselves to die, and why it happens sooner in people with degenerative brain diseases. Answers to these questions, they predict, may lead not just to treatments but to cures for these diseases that affect memory or the ability to function normally. But, those answers may still be a long way off.
In the meantime, another area of memory research is edging much closer to the finish line, with potential treatments -- if not outright cures -- tantalizingly close. This is the science of brain plasticity, or how the brain learns and stores new experiences. Tim Tully, PhD, predicts that research into brain plasticity will yield treatments for some memory-robbing diseases within the next two to five years. Tully is a founder of the privately held Helicon Therapeutics, based in Farmingdale, N.Y., and a researcher at Cold Spring Harbor Laboratories.
Switching on a 'Memory Gene'
"We've been working on one particular gene called CREB, which seems to be an important 'switch' for a [nerve cell] to decide when to form long-term memory," Tully explains. "When you experience something new, it activates a circuit in your brain [that turns on CREB]." CREB, he explains, acts like a "general contractor of the brain," organizing and directing the growth processes that strengthen the connections among nerve cells in a particular circuit of the brain. "This, we believe, is [how we form ] long-term memory."
If scientists can develop drugs that stimulate CREB, then they could strengthen the formation of long-term memories in people with diseases like Alzheimer's. "It's not going to cure [the] cell death [that caused the problem], but it'll turn up the memory formation process in the surviving [brain cells] so that the person can function better during the course of the disease," Tully explains.
Helicon Pharmaceuticals anticipates the first of its drug compounds aimed at stimulating CREB will be in early human testing before the end of the year.
Eric Kandel, MD, the Nobel laureate and memory pioneer who first discovered CREB, also believes that effective treatments for both Alzheimer's disease and age-related memory loss are in sight. But he suggests it will take between five and 10 years for researchers at Memory Pharmaceuticals, the company he founded, and other scientists to reach that goal.
He, too, believes that focusing on the genes and proteins involved in helping the brain form memories will yield unimaginable riches in terms of treatment for a variety of diseases. Research at his lab is now focused on a wide range of drugs that could act on CREB early in the memory formation process, he says. Memory Pharmaceuticals plans to start clinical trials on at least some of these drugs by the end of the year.
Treatments for Mental Retardation?
The potential of drugs that target CREB and other elements of the brain's biochemical pathways extends far beyond treating memory disorders of older adults. Could various forms of mental retardation, such as Down syndrome, be at least partially treatable? Both Kandel and Tully say yes.
"When we looked at the brains of kids with Down syndrome who died within their first year or two of life, we found to our surprise that their brains were surprisingly normal at birth. Not completely, but surprisingly close, during the first six months," Kandel says. "So it looks like the [abnormal genes that cause Down syndrome produce] their toxic effects [over] time."
He's now testing that theory in mice, trying to determine what happens if one particular gene involved in Down syndrome is turned off and no longer functions. The science is in its early stages, but he believes that blocking that gene's signals, while it won't offer a "cure," might be able to significantly reduce the damage to a person's thinking abilities. "And if you give people with Down syndrome even a somewhat better outlook, you improve life for them a great deal," he says.
Tully agrees. "There are specific [genes], known to participate in the [formation] of memory, that are defective in patients with some forms of mental retardation. Because we've developed drugs that target these genes, we may be able to treat some forms of mental retardation That's absolutely revolutionary, and it's just the beginning."
Originally published aug. 5, 2002.