Designer genes target serious diseases
Effects of aging
As if the usual insults of aging such as creaky knees and wrinkles weren't enough, it seems that old age also ushers in a reduction in an important neuropeptide called orexin (also known as hypocretin).
Orexin regulates sleep/wake cycles, cognition, and feeding and metabolism. People who suffer from narcolepsy (sudden periods of deep sleep throughout the day) have severely depleted orexin levels. Older people who experience unexplained weight loss are at higher risk for Alzheimer's disease: both might be linked to lower levels of orexin.
Jim Fadel is using a customized version of the common Lenti virus to target the hypothalamus, a region of the brain that makes orexin. His research, funded by the National Institute on Aging and American Federation for Aging Research, is testing the possibility of stimulating orexin production through virus-mediated gene therapy.
"Gene therapy started out with a lot of promise a couple of decades ago, but hit some snags. It has become a hot field again in neuroscience because of vast improvements in the ability to use specific promoters that target certain regions of the brain," Fadel said. "Our initial findings suggest virus-mediated orexin expression can improve the function of the cholinergic system, which we know plays a major role in Alzheimer's disease.
"I'm guessing that we're probably five years or more away from human trials with this particular research, but it could offer some very exciting possibilities in restoring cognitive function in those diagnosed with early-stage Alzheimer's."
The epileptic brain
After Alzheimer's disease and stroke, epilepsy is the third most common neurological disease.
It's also one of the more difficult to treat: Anticonvulsant drugs are effective for only 70 percent of those with the condition, and those drugs can cause many unwanted side effects. Treatment options for the other 30 percent range from few to none.
Funded by the National Institutes of Health, David Mott is studying the role of the excitatory neurotransmitter glutamate in epilepsy. Glutamate is used by 75 percent of all brain cells to communicate with each other. Mott is using a specialized virus to target certain glutamate receptors-called kainate receptors-that appear to play a role in the development of seizures.
In models, Mott is focusing on the hippocampus, the part of the brain that governs learning and memory and is the most common site of seizure activity.
"We're still several years away from a human trial, but we've developed a modified virus that does what it's supposed to do in the models. We're hopeful that targeting these receptors will stop seizures," Mott said.