June 2023

UNDERSTANDING GENETIC FACTORS IN PARKINSON'S DISEASE WITH STEVEN LUBBE, PHD

Episode Summary

The global prevalence of Parkinson's disease has doubled in the past 25 years. While research into this extremely diverse neurodegenerative disorder is very active, there is much left to be uncovered about the underlying cause of the disease. Recently, Northwestern Medicine investigators have discovered novel genetic factors contributing to the risk of Parkinson's disease, which may lead to potential therapeutic targets. Steven Lubbe, PhD, assistant professor of Neurology at Feinberg, discusses these findings recently published in the journal Brain.

“I hope over the next 10 to 20 years we're able to make larger inroads in identifying and understanding the causes of movement disorders across the world in all individuals.” — Steven Lubbe, PhD

Episode Notes

Lubbe discusses his work investigating the underlying cause of Parkinson's disease and other neurodegenerative disorders using large-scale genomics.

Lubbe earned a PhD in colorectal cancer genetics at the Institute of Cancer Research in London. Lubbe was motivated to shift his research from cancer to Parkinson’s disease due to the fact that his mother was diagnosed with the disease at the young age of 42.
Not a lot is known about the genetics of Parkinson's disease, and very few people who have Parkinson's disease have an actual genetic cause for the disease. About 5 to 10% of people with Parkinson's disease have a family history or are diagnosed with Parkinson's disease at a very young age.
There are only about 20 to 25 genes known to contribute to Parkinson's disease. Some well-known gene mutations, such as alpha-synuclein and LRRK2, greatly increase the risk of Parkinson's, while common genetic variants have been identified through genome-wide association studies.
Environmental factors can interact with genetics in complex ways that influence Parkinson's disease risk. Exposure to certain pesticides or heavy metals may increase the likelihood of developing the disease. However, exposure to these environmental factors does not guarantee the development of Parkinson's, as the exact relationship between exposure and disease onset remains difficult to determine.
The study of Parkinson's disease genetics has been limited to single nucleotide variants, but researchers have started investigating short tandem repeats (STRs) on a global genome level. By comparing STRs in individuals with and without Parkinson's disease, Lubb and his team found four novel genetic variants that significantly increase the risk of the disease.
They utilized data from the International Parkinson's Disease Genomics Consortium, obtaining data on 22,000 individuals with Parkinson's disease and 20,000 without. They imputed short tandem repeats (STRs) from a reference panel based on the 1000 Genomes Project. Additionally, samples were used from the Movement Disorders Center Biorepository, where Lubbe and his team have been able to look at genetics of entire families with movement disorders like Parkinson’s.
Another project central to Lubbe’s research is the genetic link between Parkinson’s and malignant melanoma. While Parkinson's disease is the loss of pigmented neurons in the brain, malignant melanoma is a cancer that involves turning melanocytes (or the cells that control how dark or how fair your skin is) into tumors.
Damage caused by Parkinson's disease starts many years before symptoms appear. Lubbe hopes that genetic research of the disease over the next 10 to 20 years might lead to earlier detection of Parkinson’s cases in individuals all over the world.

Additional Reading

Read more about Lubbe’s research on skin pigmentation and Parkinson's disease
Recent publication in Neurobiology of Aging titled: “Gene-based burden analysis of damaging private variants in PRKN, PARK7 and PINK1 in Parkinson's disease cohorts of European descent.”
More about his cancer-focused research

Steven Lubbe, PhD, Assistant Professor of Neurology in the Division of Movement Disorders, a member of Northwestern University Clinical and Translational Sciences Institute (NUCATS), and a member of the Robert H. Lurie Comprehensive Cancer Center at Northwestern Medicine.