By Staff Reports
By the time Parkinson’s is diagnosed, the disease typically has already destroyed at least half of the affected brain cells. An Oklahoma Medical Research Foundation scientist hopes to dramatically reduce that number through studies funded by a new $3 million grant.
The National Institutes of Health awarded the five-year grant to Mike Beckstead, Ph.D., to develop a way to study the disease in mice that more closely resembles Parkinson’s in humans.
Beckstead said the new model could transform Parkinson’s research, eventually leading to earlier and much more effective treatments.
In Parkinson’s, nerve cells produce less dopamine, resulting in a loss of muscle control, balance and movement. It is second only behind Alzheimer’s as the most common neurodegenerative disease, affecting an estimated 1 million people in the U.S. and 10 million worldwide, according to the Parkinson’s Foundation.
A drug known as L-DOPA, first introduced more than 50 years ago, remains the most effective treatment, but it has significant shortcomings.
“L-DOPA treats the symptoms but not the underlying cause of Parkinson’s,” Beckstead said. “The drug loses effectiveness over time, and in fact some studies have suggested that L-DOPA can actually worsen the disease.”
Beckstead’s lab studies specific neurons in the brain that produce dopamine, a chemical responsible for body movement and signaling rewards. Disruption of dopamine can produce wide-ranging consequences, from depression and addiction to Parkinson’s.
In Parkinson’s, dopamine neuron death results in symptoms that include tremors and stiffness. The root cause of this cell death, Beckstead theorizes, is a pigmentation that protects these neurons early in life but later damages them as we age.
In normal human brains, the blackish color is clearly visible when scientists study the part of the brain that includes dopamine neurons. In brains with Parkinson’s, that pigmentation is no longer evident, which signifies that most of the dopamine neurons have died, Beckstead said.
“This pigment doesn’t build up in rodent brains, and that presents a major limitation for most previous Parkinson’s studies,” said Beckstead, who holds the Hille Family Foundation Chair in Neurodegenerative Disease Research at OMRF. “Mice and rats are the traditional research models for human brain diseases, so the absence of that pigmentation has stunted our ability to understand how it may lead to Parkinson’s.”
The new research model has been genetically engineered to feature the pigmentation, Beckstead said.
His project also will involve OMRF scientist Bill Freeman, Ph.D., whose lab studies changes in how genes in the brain function as we age.
“This new mouse model will help us understand how Parkinson’s progresses in humans in a way that’s never been possible previously,” Freeman said. “That’s the key, because, ultimately, we hope future treatment consists of identifying people much earlier in the disease than we currently do and slowing the impact on someone’s independence and quality of life.”
Beckstead’s five-year grant, No. R01NS135830, was awarded by the National Institute of Neurological Disorders and Stroke, part of the NIH. He received earlier funding from the Oklahoma City-based Presbyterian Health Foundation for studies that led to the NIH grant.