Parkinson’s is a neurodegenerative disease belonging to the group of the so-called “Movement Disorders”. This pathology is slow, yet progressive and mainly affects movement and balance control.

We know that several genetic and environmental factors contribute to the development of Parkinson’s disease, but specialists do not understand the causes behind its origin completely.

Many research groups around the world are engaged in the study of this disease, and some of these groups have formed consortia. One of them is the GEoPD (Genetic Epidemiology of Parkinson Disease) consortium, which has just met at its annual convention, organized virtually by the Humanitas Congress Center.

We have discussed with Professor Stefano Duga, professor of Molecular Biology at Humanitas University and coordinator of the conference together with Dr. Alessio Di Fonzo, neurologist at the Milan Polyclinic, the topics at the center of the meeting, which was dedicated to genetics in Parkinson’s disease.

Central themes of the Conference

“The annual convention of the GEoPD consortium was held on Thursday the 15th and Friday the 16th of October. This convention brings together the main global research groups studying genetic components in Parkinson’s disease, with the goals of promoting the diffusion of information, scientific research and translational practices (i.e. the transition from research to clinical activity) in this pathology. The conference has been operating since 2004, uniting sixty groups over six continents.

The convention takes place over two days, the first attended by the members of the consortium, and the second traditionally open to everyone. We should have hosted part of the conference physically in Milan, at Humanitas, but then the epidemiological situation required resorting to the virtual mode for both days,” explains Pr. Duga.

Genetics in Parkinson’s disease

“During the first day, different consortium groups shared their progress on the projects focusing on various aspects of genetics. Some groups spoke on familial forms of Parkinson’s or the components of genetic risk in sporadic forms of the disease. We also heard on longitudinal studies that observed particular patient populations over time, studying, for instance, the evolution of the disease or the course of therapy. Other projects focused on subpopulations of patients who present forms of the disease with a clear genetic component but in which not all individuals carrying a predisposition variant develop the condition. We truly aim to understand the genetic and environmental factors that contribute to causing clinical symptoms.”

The Global Parkinson’s Genetic Program

“The second day saw the participation of scientists from outside the consortium. The day started with the presentation of the Global Parkinson’s Genetic Program (GP2) led by Andrew Singleton, a British neurogeneticist working in the United States. The program has collected DNA samples from 150,000 volunteers worldwide (patients with Parkinson’s, individuals with risk factors, and a control sample) with the aim of better understanding the genetic structure of the disease and taking some steps forward in identifying genetic risk factors.

We have to raise awareness about this five-year project, as it is an important initiative for building greater knowledge on Parkinson’s disease at a global level,” continues Pr. Duga.

Parkinson’s disease and GBA gene mutation

“Another central topic of the second day was the link between Parkinson’s disease and the GBA gene, which encodes the acid-beta-glucosidase enzyme, also called glucocerebrosidase. This gene, if mutated in both alleles, is responsible for ParkinGaucher’s disease: a lysosomal genetic disease caused by the deficiency of glucocerebrosidase found in lysosomes, small cellular organelles responsible for the degradation of cellular components that are no longer useful. The glucocerebrosidase enzyme transforms glucocerebroside, a substance that comes from degraded cells, into reusable sugars (glucose) and fats (ceramide). In individuals that have glucocerebrosidase enzyme deficiency, the glucocerebroside is not adequately transformed and therefore accumulates in the lysosomes of the macrophages, which in turn enlarge. The enlarged macrophages, called Gaucher cells, collect in particular in the spleen, liver and bone marrow, altering the functions of these organs.

A carrier of a mutation in the GBA gene in the heterozygous state (which itself does not cause Gaucher disease) has been found to have about 5 times higher risk of developing Parkinson’s, compared to the general population. Parkinson’s disease caused by variants in this gene develops earlier (about 5 years earlier than the average for Parkinson’s patients) and generally has a more rapid evolution and a greater risk of cognitive impairment. The good news, however, is that there are several clinical trials, aimed at evaluating the effectiveness of some molecules that stimulate the function of the enzyme or that, vice versa, inhibit the synthesis of its substrate (glucocerebroside),reducing the accumulation of glucocerebroside in the central nervous system.”

Professor Duga, together with Dr. Di Fonzo presented the studies, currently underway in Milan, that aim to understand genetic risk factors that modulate the clinical manifestations of the disease. This information is essential to identify individuals at greatest risk of developing Parkinson’s and to intervene early with personalized therapies based on the molecular data of the individual patient. Dr. Pablo Sardi (from Sanofi) concluded the convention with an interesting overview of the ongoing clinical trials, which present important prospects for the treatment of Parkinson’s patients.

“These were interesting and lively two days that gave many young students and researchers an opportunity to present their work to an international audience: it was a moment of significant growth for them, of which we are very proud. I thank all the participants and all those who spent their time at the Humanitas Congress Center for the success of the event,” concluded Professor Duga.