Researchers win Breakthrough Prize for genetics discoveries
Awards are result of work on LRRK2, GBA1 genes in Parkinson's disease
The 2024 Breakthrough Prize in Life Sciences has been awarded to three researchers who made groundbreaking discoveries related to the genetic causes of Parkinson’s disease.
Breakthrough Prizes, popularly called the “Oscars of Science,” honor researchers who’ve made impactful discoveries across the life sciences, fundamental physics, and mathematics. There were 11 awardees this year, eight in life sciences for advances in Parkinson’s, cancer, and cystic fibrosis.
“Humanity’s collective intelligence is our most significant achievement,” Yuri Milner, a founding sponsor of the Breakthrough Prize, said in a press release from the Breakthrough Prize Foundation. “Great scientists, and Breakthrough Prize laureates among them, are at the forefront of this incredible phenomenon in our Universe.”
Parkinson’s research winners are Ellen Sidransky, MD, of the U.S. National Human Genome Research Institute, National Institutes of Health (NIH); Thomas Gasser, MD, PhD, of the Hertie Institute for Clinical Brain Research, University of Tübingen, Germany; and Andrew Singleton, PhD, of the National Institute on Aging, NIH.
Gasser and Singleton’s research identified mutations in the LRRK2 gene as a significant genetic cause of Parkinson’s. Sidransky won for identifying the link between GBA1 mutations and the neurodegenerative disease. The discoveries were made in part on their own and partly in a collaboration between the scientists, who will share a $3 million prize.
“Our findings on the LRRK2 and GBA1 genes provide approaches for treatments targeting molecular causes, which are being pursued in various ways,” Gasser, chairman of the board at the Hertie Institute for Clinical Brain Research and medical director of neurology at the University Hospital Tübingen, said in a separate press release. “I am confident that one day it will be possible to prevent Parkinson’s or at least delay the onset of the disease and slow its progression.”
Significance of research on genes
LRRK2 is important for various nerve cell processes, including making sure the cells have enough energy to work properly. Both LRRK2 and GBA1 are key for recycling cellular waste to sustain normal cellular function.
LRRK2’s resulting enzyme, LRRK2, is thought to be overactive in Parkinson’s patients, suppressing cells’ ability to clear waste, causing abnormal proteins to build up to toxic levels and disrupt nerve cell function. GBA1 mutations, which cause the enzyme beta-glucocerebrosidase to malfunction, are thought to also impair cellular waste clearance.
“Each of these genes contains the blueprint for a specific enzyme,” Gasser said. “The mutations cause these enzymes to not function optimally. The bottom line is that they cause damage.”
Mutations in the two genes are understood to be among the most common genetic risk factors for Parkinson’s. They can lead to familial forms of Parkinson’s, but certain genetic variants can also be risk factors for sporadic, or nonfamilial Parkinson’s.
“Our studies have shown that genetic factors also play an important role here,” Gasser said. “Although they are not singular causes of Parkinson’s, they are nevertheless significant, for example, for the risk of disease, the age of onset or disease severity.”
Understanding these genes play a role in the disease, and how they do so, means scientists can focus on developing more targeted treatments.
“Currently available therapies only have a symptomatic effect and do not address the roots of the disease,” Gasser said, noting “they cannot stop the brain’s degradation and sooner or later lose their efficacy.”
Research into LRRK2, GBA1 genes
Efforts are underway to develop LRRK2 suppressors to prevent the detrimental effects of LRRK2 mutations.
Gasser and his colleagues are planning a clinical trial for people with GBA1-associated Parkinson’s that’s slated for next year. They’ll use antibodies to target protein deposits that cause damage in the Parkinson’s brain.
“People with GBA1 mutation tend to develop a particularly severe form of Parkinson’s. They often develop dementia relatively early in the course of the disease,” Gasser said. “We want to investigate whether we can prevent or at least delay mental decline. This means that we aim to provide preventive treatment before symptoms of dementia manifest. Although this would not eliminate the motor disorders, it would make a significant contribution to the quality of life.”
Gasser and his international collaborators are also working to identify new genetic causes of Parkinson’s, which may differ by geographical region or in certain populations.
“From this, we expect to gain insights not only into the familial form of Parkinson’s, but also into the nonhereditary, so-called sporadic variant,” Gasser said.
Award winners will be honored at the annual Breakthrough Prize Ceremony in Los Angeles next April.
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