UAB Synopsis, Vol. 26, No. 18, May 14, 2007

Protecting and Restoring Brain Function
The Center for Neurodegeneration and Experimental Therapeutics (CNET), established by the University of Alabama System Board of Trustees in February, investigates treatments for neuro- degenerative diseases, translates new discoveries rapidly and safely into clinical care, and educates scientists and clinicians about this group of common and disabling disorders, says Professor of Neurology and CNET Director David G. Standaert, MD, PhD. Dr. Standaert is the inaugural holder of the John T. and Juanelle D. Strain Endowed Chair in Neurology and directs the Department of Neurology’s Division of Movement Disorders.

New Knowledge and Novel Animal Models
Rapidly advancing genetic knowledge, particularly the identification of genes involved in neurodegenerative diseases, is driving development of animal models that are helping neuroscientists dissect underlying pathogenic mechanisms of these disorders. “The first gene for Parkinson’s disease was identified about a decade ago,” Dr. Standaert says. “It’s a rare gene that’s found almost exclusively in families in southern Italy. Although as much as 95% of Parkinson’s disease is sporadic, the identification of this gene allowed scientists to pinpoint an abnormal protein that produces a range of neuropathic changes and appears to play a role in all cases of the disease, not just inherited forms.”

The discovery of that protein led to a novel mouse model, which helped scientists find other genes involved in Parkinson’s disease. Investigators have now identified six genes implicated in the disease. “Once scientists made a crack in the problem, it opened the door to a cascade of events — the discovery of other abnormal proteins and the development of a number of unique animal models that are helping neuroscientists search for therapies that might slow or alter disease progression.”

Genetic breakthroughs are occurring across the spectrum of neurologic diseases. The discovery of genes involved in inherited forms of Alzheimer’s disease has led to insights into the far more common sporadic cases, and identification of 11 genes that cause dystonia is advancing understanding of that group of disorders.

Neuroprotection, Neurorestoration
Despite many advances, management of neurologic diseases such as Parkinson’s and Alzheimer’s is still aimed at symptom control. Fueled by new mechanistic knowledge of neurodegenerative diseases, CNET scientists and others are shifting their focus toward protecting and enhancing the function of healthy neurons. “By the time Parkinson’s disease becomes symptomatic, patients have lost 50% to 70% of their dopamine-producing neurons,” Dr. Standaert says. UAB is currently enrolling patients in several trials of neuroprotective agents, including NIH-funded studies of creatine and Coenzyme Q10, as well as industry-funded studies of rasagiline and other agents that may defend remaining neurons from the disease process.

CNET scientists are seeking viable strategies for neurorestoration, which could potentially regenerate brain function by stimulating cell growth and neural connections. “Research has shown that nerve growth factors have neuroprotective properties, as well as some restorative action,” he says. “The challenge is delivery — pumping growth factor directly into the brain has not worked well, but transporting it via viral vectors may produce better results.”

With input from scientists from multiple disciplines, including neurobiology, cell biology, genetics, and the clinical neurosciences, CNET is integrating basic and clinical activities to advance treatment for costly and devastating neurological diseases, which will likely skyrocket in incidence as the population ages.

“Neurodegenerative diseases, while distinct in their symptoms, share many common mechanisms,” Dr. Standaert says. “CNET scientists are building on new knowledge to develop treatments that will slow or reverse the brain degeneration underlying these disorders.”

CNET, located on the fifth floor of the Civitan International Research Center, is equipped with state-of-the art facilities for molecular, biochemical, and anatomical studies of animal and cellular disease model systems.

For more information about ongoing investigations or postdoctoral training opportunities, contact Dr. Standaert at 205.996.6329 or through the CNET Web site, www.uab.edu/CNET.