The next 10 years are critical for therapeutic Parkinson’s research!
March 3, 2021 – “Parkinson’s scientists believe that we could have the first causative therapies in use by 2030. This will enable us to slow the progression of Parkinson’s disease and other movement disorders or even prevent their occurrence,” states Prof. Günter Höglinger, MD. He is Director of the Neurological Clinic at the Hanover Medical School and First Chairman of the German Society for Parkinson’s Disease and Movement Disorders (DPG). Höglinger called today to the virtual live congress “Parkinson and Movement Disorders – Highlights Digital” the overall social and political will to fight these diseases more consistently. Science now has the necessary know-how.
What is missing is the stringent promotion and structuring of this medical research. “With the Parkinson’s Agenda 2030, we want to sensitize the public to the realistic and hopeful option that these significant neurological diseases could finally be treated causally 200 years after they were first described,” Höglinger said.
Medical progress is feasible – if we want it to be
What medical research can achieve has been demonstrated by the successful development of numerous vaccines against the SARS-CoV-2 virus in just a short time, including Biontech/Pfizer’s mRNA vaccine technology, which was used for the first time for a vaccination. The decisive factors were the pressure to succeed created by the pandemic, the high level of investment, including from the public sector, and the prospect of refinancing the development costs for the companies. In the case of Parkinson’s and other movement disorders, on the other hand, public attention, available funding and the collective will to solve the problem in a timely manner are significantly lower.
“Yet research with new technologies such as biomarkers, genetic stratification and molecular therapies could also usher in a revolution in the treatment of Parkinson’s disease and other movement disorders over the next decade,” Professor Höglinger said. In recent decades, medicine has successfully developed symptomatic therapies for patients that lead to symptom relief. These are very important for the affected patients. But they do not delay the progression of the disease or even prevent its onset. Yet Parkinson’s disease and other movement disorders are of great social relevance. In Germany alone, around 400,000 patients are affected by Parkinson’s disease. Worldwide, the number of patients diagnosed has risen from 2.5 million in 1990 to 6.1 million in 2016, especially in the industrialized nations. With the trend continuing to rise.
Parkinson’s Agenda 2030 aims to raise awareness of health and research policies
“There is a lack of sustained political will to translate the findings from basic research into the development of new therapies for Parkinson’s and other movement disorders in a timely manner now. This requires an effort by society as a whole, because individual research groups cannot succeed on their own,” says Höglinger. Germany is one of the leading international locations for Parkinson’s research. There are excellent regional and national research networks. However, their organization and funding is largely up to the researchers themselves. They are forced to shimmy from research proposal to research proposal, he said. “The research potential is there, but progress in developing causal therapies is far too slow,” Höglinger said.
Early detection is key to developing preventive therapies
Years or even decades usually pass between the onset of the disease in the body and the appearance of the first clinical symptoms in Parkinson’s or other movement disorders. This window of time provides the opportunity to detect the disease before it affects patients. To identify these sufferers without symptoms, scientists now have olfactory tests, sleep studies, skin biopsy tests, neural fluid studies and genetic diagnostics at their disposal. A new molecular method for the objective diagnosis of Parkinson’s syndromes is, for example, the determination of alpha-synuclein aggregates in the cerebrospinal fluid by RT-QuiC or of tau aggregates in the brain with the PET tracer PI-2620. For these individuals at risk of Parkinson’s disease, ways must be sought to prevent the onset of clinical symptoms through early intervention.
Neurogenetics enables differentiated strategies
Parkinson’s disease has not one but several known causes. Many genetic variants that have now been identified influence the risk of Parkinson’s disease. A key to success in therapy development is a precise understanding of those molecular signaling pathways involved in disease development. Numerous international projects, many of them under German leadership, are on the way to clarifying this issue. These include the Rostock International Parkinson Disease (ROPAD) study to determine the genetic epidemiology of Parkinson’s disease and the Lübeck International Parkinson’s Disease (LIPAD) study to investigate genetic and environmental modifiers of penetrance and expressivity. The different genetic variants that can be identified open up the possibility of tailored therapies for individual patients. This “precision medicine” is already successful in cancer therapy, for example.
Particularly in the case of such heterogeneous diseases as Parkinson’s syndromes, science needs a much more comprehensive and standardized clinical, biochemical and genetic typing of the different disease variants. The goal must be to establish patient cohorts that can be rapidly recruited nationwide for testing new clinical therapeutic approaches (trial-ready cohorts). “It consumes many months, sometimes years, to find suitable patients for each new clinical trial. These are usually highly motivated to participate in trials. The big challenge is matching suitable subjects and suitable trials,” Höglinger said. Fortunately, the DPG and the German Center for Neurodegenerative Diseases (DZNE), for example, have initiated limited cohort studies with Parkinson’s patients. The larger goal, however, must be to establish a national Parkinson’s registry similar to existing cancer registries and to maintain it in the long term.
Numerous new therapeutic approaches at the molecular level
Research for patients with Parkinson’s disease and other movement disorders in Germany is also very active in the field of therapy development. Only three years ago, the first people with the rare movement disorder chorea Hungtington were successfully treated with the novel antisense oligonucleotide therapy. This group of substances suppresses the production of misfolded proteins based on defective genes (“gene silencing”). The method is now also being used in clinical trials in Germany to treat Parkinson’s syndromes. Another example of novel molecular therapy strategies are numerous studies with monoclonal antibodies, for example against alpha-synuclein or tau protein, which are causally associated with Parkinson’s syndromes. For example, a study with the alpha-synuclein antibody prasinezumab in Parkinson’s has recently yielded promising interim results that warrant further development.
The Mission of the German Parkinson’s Disease and Movement Disorders Society
Under the title of the Parkinson’s Agenda 2030, the professional organization is now devoting more attention to the scientific and societal challenges described above. Within the framework of intensified public relations work, sensitization and activation of society for the concerns of patients with Parkinson’s disease and other movement disorders are to be achieved. At the same time, the national funding landscape for research into the causes and treatment options is to be significantly improved. As an important building block for this, the DPG has initiated the Parkinson Foundation (www.parkinsonstiftung.de). Furthermore, the DPG supports research into the causes, early and differential diagnosis and new treatment options with its working groups. A national registry for Parkinson’s disease and other movement disorders is established and supported. In particular, emphasis will also be placed on optimizing the national research landscape for clinical testing of new therapeutic approaches with patients.
These concerns serve one goal: to advance the development of new therapies for Parkinson’s disease and other movement disorders over the next 10 years to the first causal therapy.
Prof. Dr. med. Günter Höglinger
1st Chairman of the DPG, Director of the Clinic for Neurology, Hannover Medical School
The German Society for Parkinson’s Disease and Movement Disorders (DPG) promotes research into Parkinson’s disease and improves patient care. Organized in the scientific-medical society are Parkinson’s physicians as well as basic researchers. The cooperation of these two branches is crucial for progress in diagnostics and therapy.