NEW MECHANISMS

Filed Under News 

Advances in Possible Treatments for Gaucher and Parkinson’s Diseases

 

Gaucher disease affects an estimated 1 in 50,000 to 1 in 100,000 people in the general population. People of Eastern and Central European (Ashkenazi) Jewish heritage are more likely to get Gaucher disease. Parkinson’s disease affects 1.5-2% of people over age 60, and the incidence increases with age. In the United States, about 60,000 new cases are identified each year. Parkinson’s disease affects more than 1 million people in North America and 7-10 million people worldwide.

 

Gaucher disease occurs when GBA1, the gene that codes for the protein glucocerebrosidase, is mutated. This protein normally helps cells dispose of certain fats (lipids), a type of waste produced by all cells. When a person inherits two mutated copies of GBA1, lipids accumulate and can cause symptoms such as enlargement of the spleen, frequent bleeding and bruising, weakened bones and, in the most severe cases, neurological disease. People with even one mutated copy of GBA1 are at higher risk of developing Parkinson’s disease, a common disorder characterized by tremors, muscular rigidity and slowed movements.

 

According to an article published on line (12 June 2016) in the Journal of Neuroscience, with assistance from a high tech robot known at Tox21, National Institutes of Health researchers have identified and tested a molecule that shows promise as a possible treatment for Gaucher disease and Parkinson’s disease.

 

To better understand the connection between Gaucher and Parkinson’s diseases, the authors used a labor-intensive technology to develop pluripotent stem cells (unspecialized cells that can develop into various specialized body cells). The stem cells were created in the lab from the skin cells of Gaucher patients with and without Parkinson’s disease. The stem cells were then converted into neurons that had features that were identical to those in people with Gaucher disease. Results showed that the neurons from Gaucher patients, who also had Parkinson’s disease, had elevated levels of alpha-synuclein. This is the protein that accumulates in the brains of people with Parkinson’s disease impacting neurons responsible for controlling movement.

 

The authors then looked for a molecule that would help patients with mutant GBA1 break down cellular waste. In a process known as high-throughput drug screening, the authors used the Tox21 robot to evaluate hundreds of thousands of different molecules. The authors identified a promising molecule, NCGC607which helps to “chaperone“ the mutated protein so that it can still function. In the patients’ stem cell-derived neurons, NCGC607 reversed the lipid accumulation and lowered the amount of alpha-synuclein, suggesting a possible treatment strategy for Parkinson’s disease.

 

Daniel Kastner, M.D., Ph.D., NHGRI scientific director and director of the institute’s Division of Intramural Research said that “This research constitutes a major advance as it demonstrates how insights from a rare disorder such as Gaucher disease can have direct relevance to the treatment of common disorders like Parkinson’s disease.“ the authors will next test the new molecule to see if it might be developed into an appropriate prototype drug for patients with Gaucher disease and Parkinson’s disease.

 

Comments

Leave a Reply

You must be logged in to post a comment.