Three million dollars for Parkinson research at the DZNE

Studies on the “gut-brain axis”: Bonn and Tübingen receive 1.5 million US dollars each in funding

Bonn/Tübingen (Germany), November 30, 2020. The German Center for Neurodegenerative Diseases (DZNE) has been awarded a research grant of three million US dollars by the US initiative “Aligning Science Across Parkinson’s” (ASAP). Funding will be equally divided between the DZNE sites in Bonn and Tübingen. Investigators will study the role played by the gut flora in modulating Parkinson genetic risk factors and promoting alpha-synuclein pathology associated with the disease. This project is part of a collaborative effort involving partners in the UK, France and Italy. Research outcomes will help elucidate disease mechanisms, evaluate criteria for individualized medicine and provide new clues for therapeutic intervention.

Parkinson’s is a brain disease characterized by motor as well as non-motor symptoms. At the microscopic level, it features the degeneration of specific neuronal cell populations and intraneuronal accumulation of a protein, alpha-synuclein, in an aggregated form. The cause of the disease remains unknown, although specific gene variations can increase disease risk. Mutations in the gene coding for the enzyme glucocerebrosidase (GBA) are the commonest known genetic risk factor for Parkinson’s disease. Interestingly, however, carriers of these mutations do not always develop the disease, may develop the disease at different ages and be affected by more or less severe clinical manifestations. Therefore, disease conversion and progression in GBA mutation carriers is modulated by other, still undiscovered factors.

The “gut-brain axis”

Increasing evidence from a wide spectrum of observations supports the possibility that alpha-synuclein pathology affects the gut and may travel from the gut to the brain, and vice versa, via a “gut-brain axis”. This axis involves nervous connections as well as endocrine and immune signaling. The assembly of microorganisms colonizing the gut – called gut microbiome or gut flora – has been suggested to play an important role in the development of alpha-synuclein pathology in the gut and its subsequent spreading to the brain. Inter-personal variability of the gut flora could therefore make different individuals more or less susceptible to Parkinson’s disease development.

“We intend to investigate how all these pieces of the puzzle may fit together. Our hypothesis is that the microbiome of Parkinson patients with a GBA mutation differs from the microbiome of individuals who carry the mutation but do not develop the disease. We will also investigate specific mechanisms that could explain this link between variations in the microbiome and disease development. These mechanisms may become targets of new anti-Parkinson therapeutics,” said Donato Di Monte, research group leader and coordinator of this project at the DZNE in Bonn.

“It is known that several factors affect the gut flora, such as genetic factors, diet and medications,” said Michela Deleidi, research group leader at the DZNE’s Tübingen site. “If we understand how these factors influence the gut-brain axis and if we specifically act on the microbiome, it may be possible to reduce the risk of Parkinson’s disease or improve disease symptoms.”

An international team effort

“This research effort is truly inter-disciplinary and highly translational, facilitating the flow of new information from the laboratory to the clinic and from the clinic to the lab. It will benefit from close interactions between clinical and fundamental researchers with complementary expertise in the UK, France, Italy and Germany,” Di Monte said. Patients will primarily be recruited and monitored in the UK and Italy, microbiome analyses will mostly be done in France and studies on disease mechanisms using a variety of experimental models are centered in Bonn and Tübingen.

“By investigating the link between genetic, environmental factors, and the gut microbiome, our research will represent a step toward precision medicine, that is interventions that are specifically tailored to the individual”, Deleidi said.

“An important consideration regarding this project is that the new findings in Parkinson patients with GBA mutations will bear important implications for all patients affected by Parkinson’s disease. Indeed, the gut-brain axis could play a role in disease onset and progression in all Parkinson patients,” Di Monte concluded.

The ASAP initiative - working with its implementation partner The Michael J. Fox Foundation for Parkinson’s Research – has awarded a total of over eight million US dollars to the research institutions collaborating on this project. These institutions are University College London (London), INRAE (Paris), Fondazione Mondino (Pavia) and DZNE (Bonn/Tübingen).

 

 

On the German Center for Neurodegenerative Diseases (DZNE)

Research at the DZNE (fundamental and clinical research, population studies and systems medicine) investigates all aspects of neurodegenerative diseases in order to develop novel approaches of prevention, treatment and health care. DZNE’s investigators at ten sites across Germany cooperate closely with university laboratories, university hospitals, and other national and international institutions. The DZNE is a member of the Helmholtz Association.

Symbolic image of a neuron.

In Parkinson’s disease, certain proteins accumulate within neurons. Symbolic image - not for editorial use. Source: Kateryna_Kon - stock.adobe.com

Media relations

Dr. Marcus Neitzert
Press
marcus.neitzert@dzne.de
 +49 228 43302-267

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