Sidransky and Singleton Win the Prestigious Breakthrough Prize

BY NIH CATALYST STAFF

NIHers Ellen Sidransky and Andrew Singleton have won the 2024 Breakthrough Prize in Life Sciences for their impactful scientific discoveries of the most common genetic causes of Parkinson's disease. They share this prestigious recognition with Thomas Gasser of the Hertie Institute for Clinical Brain Research in Tuebingen, Germany.

The Breakthrough Prize Foundation made the announcement on September 14, 2023. The citation reads: “ For identifying GBA1 and LRRK2 as risk genes for Parkinson’s disease, implicating autophagy and lysosomal biology as critical contributors to the pathogenesis of the disease.”

Sidransky is Chief and Senior Investigator in the Medical Genetics Branch at the National Human Genome Research Institute. She identified mutations in the gene GBA1, which encodes an enzyme that breaks down fatty substances in cells, as a genetic risk factor for Parkinson's.

Sidransky’s discoveries in Parkinson's disease began through her long-term investigations into another disorder, Gaucher disease, a rare genetic condition that can present in childhood or adulthood and is caused by a disruption in cells' ability to break down fatty molecules. In symptoms and development, Parkinson's disease is vastly different from Gaucher disease, but her discovery of genetic links between these conditions could help develop future treatments for both diseases.

A patient of Sidransky's with Gaucher disease developed early-onset Parkinson's disease, leading her to wonder whether there was any connection between these two conditions. Sidransky then identified other patients with Gaucher disease who had Parkinson's disease and also found that many of her patients with Gaucher disease had family members with Parkinson's disease.

Sidransky's research story is relayed, in part, in her 2020 Wednesday Afternoon Lecture Series (WALS) Astute Clinician Lecture, “Gaucher Disease: How a Rare Disease Provides a Window into Common Neurodegenerative Disorders,” archived at https://videocast.nih.gov/watch=38966.

Singleton is an NIH Distinguished Investigator in the National Institute on Aging and Director of the NIH Intramural Center for Alzheimer’s and Related Dementias. He leads a worldwide team of researchers who study the genetics behind Parkinson's disease and other neurodegenerative disorders.

He and Gasser independently demonstrated that mutations in the LRRK2 gene result in increased activity of a protein believed to contribute to neuronal damage in the disease. These discoveries offer clues to the disease mechanism, pointing to the role of the lysosome, the cellular organelle that degrades and recycles cellular components.

More specifically, Singleton's group discovered several genetic mutations that cause disease, including the alpha-synuclein multiplication mutation and mutations in LRRK2. Indeed, his laboratory has identified most of the known genetic risk factors for Parkinson's disease. He was a founding member of the International Parkinson Disease Genomics Consortium and the Global Parkinson's Genetics Program.

Singleton's research story is relayed, in part, in his 2021 WALS G. Burroughs Mider Lecture, “Leveraging the Intramural Research Program to Effect Foundational Progress in Neurodegenerative Disease,” archived at https://videocast.nih.gov/watch=44237.

Established in 2012, the Breakthrough Prize comprises a set of international awards bestowed in three categories: Mathematics, Fundamental Physics, and Life Sciences. Gasser, Sidransky, and Singleton will share a $3 million award. More information about the 2024 Breakthrough Prize is at https://breakthroughprize.org/News/83.