Opening a new door to Parkinson's disease

A nationwide consortium of scientists at 20 institutions, led by HSCI Principal Faculty member Ole Isacson, PhD, has used stem cells to take a major step toward developing personalized medicine for the treatment of Parkinson's disease. "This is the first comprehensive study of how human neuronal cells can be models of Parkinson's, and how it might be treated," said Isacson.

In part supported by the Harvard Miller Consortium for the Development of Neurosystem Therapies, the team of scientists used induced pluripotent stem cells (iPS cells) that had been obtained from the skin cells of patients carrying genetic mutations implicated in Parkinson's disease, and used those cells to derive neural cells, providing a platform for studying the disease in human cells outside of patients.

In a paper published in the journal Science Translational Medicine, the researchers report that although approximately 15 or so genetic mutations are linked to different forms of Parkinson's, many seem to affect the mitochondria, the cell units that produce most of a cell's energy.

The researchers determined that certain compounds or drugs could reverse some signs of disease in the cultured cells with specific genetic mutations and not in cells with other types of mutations, making real the concept of developing specific drugs for specific patient populations.

The study was launched with federal stimulus funding provided by the National Institutes of Health (NIH) and was continued with funding from HSCI through the Miller Consortium.

"These findings suggest new opportunities for clinical trials of Parkinson's disease, wherein cell reprogramming technology could be used to identify the patients most likely to respond to a particular intervention," Margaret Sutherland, PhD, a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS), said in a press release.

The new research indicates that compounds that previously have shown promise in treating Parkinson's in animal studies have differing levels of effectiveness on different genetic forms of Parkinson's, and the hope is that such findings can be the basis for more specific drugs for individuals with sporadic forms of Parkinson's. As Isacson explained in an interview, this latest study points the way to screening patients with Parkinson's for their particular variation of the disease, and then treating them with drugs shown to work on that specific variation, rather than trying to treat all patients with the same drugs, as is generally done now.

"We believe that using human stem cells to study the disease is the correct way to go," Isacson said. "If we have the cell type most vulnerable to the disease in a dish, we can study those cells and compare them to the least vulnerable cells. Traditionally in neurology," he said, "all patients with the same disease get the same drugs, but they may have the disease for different reasons. This gives us a way to tease out those different reasons and find different ways to treat them."

Isacson's colleagues in the consortium project are HSCI faculty Kevin Eggan, PhD, Paola Arlotta, PhD, and Lee Rubin, PhD.