Tübingen Parkinson’s Researchers Receive World’s Largest Science Award

The Tübingen Parkinson researcher Prof. Dr. Thomas Gasser will receive the $3 million “2024 Breakthrough Prize in Life Sciences ” together with a scientist who both work in the USA. The three experts are being honored for the discovery of genetic risk factors for Parkinson’s disease. At least 200,000 people in this country are affected by this previously incurable nerve disease. The “ Breakthrough Prize.”is awarded in various subject areas and is considered the world’s most valuable award in the natural sciences. This time, among other things, significant advances in the treatment of cancer and cystic fibrosis will also be recognized. Thomas Gasser conducts research in a leading position at the Tübingen site of the German Center for Neurodegenerative Diseases (DZNE) and is chairman of the board of the Hertie Institute for Clinical Brain Research at the University of Tübingen. He is also medical director of the neurology department with a focus on neurodegenerative diseases at the University Hospital of Tübingen.

When Parkinson’s disease occurs, certain nerve cells in the brain that produce the neurotransmitter dopamine die. The resulting lack of dopamine causes movement disorders such as tremors, slow movements, muscle stiffness and problems with balance. In the advanced stages of the disease, some patients also develop dementia. Why these brain cells die is still not fully understood. Thomas Gasser as well as Ellen Sidransky and Andrew Singleton , the latter both researching in the USA, discovered in the 2000s that mutations (deviations from the normal form) in certain genetic genes increase the risk of Parkinson’s disease, and some mutations even inevitably trigger the disease. The “ Breakthrough Prize in Life Sciences“ recognizes these pioneering achievements: They have expanded the understanding of the molecular mechanisms of Parkinson’s disease and paved the way for studies in which new therapy concepts are currently being investigated. These groundbreaking findings about genetic risk factors for Parkinson’s were developed partly independently and partly in collaboration between the award-winning researchers.

Damaging enzymes
The mutations in question affect the genes LRRK2 (pronounced “LARK2”) and GBA1. “Each of these genes contains the blueprint for a specific enzyme. Due to the mutations, these enzymes do not function optimally. “In the end, they cause damage,” explains Thomas Gasser. “The consequences are serious. LRRK2 is involved in various processes within nerve cells; among other things, it ensures that the cells’ power plants function correctly and provide energy. On the other hand, both LRRK2 and GBA1 are important for the recycling and elimination of waste products from cellular metabolism.” The gene mutations described are, on the one hand, relevant for the hereditary (“familial”) form of Parkinson’s disease, in which the affected people occur in every family generation inevitably fall ill – often before the age of 50. Age. On the other hand, some of these genetic variants are also risk factors for the much more common “sporadic” form of Parkinson’s, which typically occurs over the age of 60 and whose trigger cannot be clearly identified.

Prospects for therapy
There is currently no cure for Parkinson’s disease. However, the symptoms can be treated and alleviated quite well for a certain period of time. It is often even possible to keep the effects of the disease at bay for years, so that the affected people are only slightly restricted in their everyday lives. “However, the currently available therapies only have a symptomatic effect and do not address the roots of the disease. “That’s why they can’t stop the breakdown processes in the brain and sooner or later lose their effect,” says Gasser. “However, our findings about the LRRK2 and GBA1 genes provide starting points for treatments that target molecular causes and that are being pursued in various ways. I am confident that one day it will be possible

New approaches
In fact, the pharmaceutical industry is working on inhibitors to slow down the mutated LRRK2 enzyme and its harmful effects. In Tübingen, Gasser and colleagues are currently preparing a clinical study aimed at patients with Parkinson’s disease and the GBA1 mutation. “People with a GBA1 mutation usually suffer from a particularly severe form of Parkinson’s. They often develop dementia early in the course of the disease. We want to investigate whether we can prevent or at least delay mental decline. So we want to treat preventatively before symptoms of dementia become noticeable. Although this would not eliminate the motor disorders, it would still make a significant contribution to the quality of life. To do this, we want to use antibodies to combat certain deposits, which accumulate in the brain during Parkinson’s disease. The clinical tests are scheduled to begin next year,” says Gasser.

Votes for the award
Prof. Dr. Bernd Pichler, Dean of the Tübingen Medical Faculty: “We are delighted about the award from Prof. Dr. Thomas Gasser with the Breakthrough Prize for his groundbreaking Parkinson’s research. Prof. Gasser is an outstanding figure in neurology and a respected scientist on an international level, which is demonstrated by this novel award. His groundbreaking work has deepened our understanding of Parkinson’s disease and advanced innovative treatment approaches. Prof. Gasser impressively illustrates Tübingen’s research focus in the field of neurology and we are proud of his success.”

“We as the Hertie Foundation are also very proud of this special honor for Prof. Gasser. We are firmly convinced that thanks to the unique structure at the Hertie Institute for Clinical Brain Research, which we support, Mr. Gasser was able to do excellent clinical work and, at the same time, carry out his groundbreaking research on Parkinson’s disease,” says Frank-Jürgen Weise, CEO of the Hertie Institute. Foundation, endowment.

“Thomas Gasser has long been at the forefront of world research and has contributed to a better understanding of Parkinson’s disease and other neurodegenerative diseases,” said Prof. Dr. Pierluigi Nicotera, CEO of the DZNE. “Prof. Gasser is an outstanding leader, he has fostered the development of many clinical scientists, and his work has been crucial in the design of new, personalized treatments that will help defeat Parkinson’s disease in the future.”

International cooperation
The mutations in the LRRK2 and GBA1 genes are among the most common genetic risk factors for Parkinson’s that are now known. However, experts suspected that there are others – as yet undiscovered. Gasser’s Tübingen team is therefore participating in international research projects in which the genetic makeup of thousands of people with Parkinson’s is examined. “Some of the genetic risk factors that have now been found are not evenly distributed. Globally, there are differences in their frequency between population groups and regions. Such findings are important for the development of individualized therapies and can only be achieved through international collaboration,” says Gasser. “We hope this will provide us with insights not only into the familial form of Parkinson’s, but also about the non-hereditary, i.e. the so-called sporadic variant. Our studies show that genetic factors also play an important role here. Although they are not the sole determining causes of Parkinson’s, they are still significant, for example for the risk of the disease, the age at onset or the severity of the disease.”

background
Parkinson’s is the second most common neurodegenerative disease after Alzheimer’s. It manifests itself particularly through movement disorders and usually occurs in older adults: the vast majority of those affected are at least 60 years old. In many cases, it is possible to alleviate the symptoms of the disease with medication and physiotherapy over a period of years before current therapies lose their effectiveness due to the steadily progressing brain damage. There is still no cure for the disease to this day. In Germany, at least 200,000 people are affected by Parkinson’s disease, and the number is rising.