Mount Sinai researchers uncover new genetic drivers of Parkinson's disease

Nov 22, 2019

Defects in the STMN2 gene cause nine other genes related to Parkinson's disease to become overly active, a new study reports. (CC0 Creative Commons)

Only about 20% of Parkinson’s diagnoses can be tied to genetic mutations, making the disease difficult to address with targeted therapies. Researchers at the Mount Sinai Icahn School of Medicine hope to change that by using brain samples from Parkinson’s patients to identify gene networks that drive the disease.

A new study out of Mount Sinai takes that effort one step further.

The Mount Sinai scientists examined postmortem analyses from 83 patients in eight studies and identified the gene STMN2 as a key regulator of Parkinson’s disease. They went on to show that when the gene is knocked down in the brains of mice, nine other genes that had been previously tied to Parkinson’s became overly active. They published the finding in the journal Nature Communications.

"The new genes we identified suggest that new pathways should be considered as potential targets for drug development,” particularly for Parkinson's cases that have no known cause, said Zhenyu Yue, Ph.D., Professor of Neurology and Neuroscience at the Icahn School, in a statement.

The team focused in on the substantia nigra, the region of the brain that’s most negatively affected by Parkinson’s. They compared brain tissue from the 83 patients to tissue taken from 70 people who had been healthy. They then applied a statistical method called multiscale gene network analysis (MGNA) to both sample sets, which allowed them to identify gene networks associated with Parkinson’s.

n healthy people, the STMN2 gene is expressed in neurons that produce dopamine, the critical neurotransmitter that’s lacking in the brains of people with Parkinson’s. When they knocked down STMN2 in the substantia nigra of mice, the animals struggled to complete motor tasks, such as balancing on a rod. Their dopamine-producing neurons started to break down, and there was an increase in a toxic protein called alpha-synuclein in their brains, the Mount Sinai team reported.

The STMN2 gene is of great interest to researchers studying neurodegenerative diseases. Earlier this year, a Harvard team reported a newly discovered connection between STMN2 and TDP-43, a gene that’s mutated in some cases of amyotrophic lateral sclerosis (ALS). They’re now examining whether repairing the STMN2 gene can slow or stop the progression of ALS.

The next step for the Mount Sinai researchers is to validate their observations related to STMN2 and Parkinson’s disease in larger studies. “Our approach is expected to be improved with comprehensive longitudinal studies, increased sample size, and better diagnosis” of Parkinson’s, they wrote in the study.

https://www.fiercebiotech.com/research/mount-sinai-researchers-uncover-new-genetic-drivers-parkinson-s-disease