G-QUEST – GBA-Quebec Study Group – Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, with a prevalence of 1-2% of the population over the age of 60. As the world’s population ages, the number of PD patients in 2050 is projected to be 25-50 million. Since PD is a long, slowly progressive disease, the financial, social, psychological and health implications are huge.

GBA Mutations and Activity in Parkinson’s Disease

Mutations in GBA are the most common genetic risk factor for Parkinson’s disease (PD), and the enzymatic activity of glucocerebrosidase, the enzyme encoded by GBA, is often reduced – even in PD patients without GBA mutations. Understanding the function and dysfunction of GBA in Parkinson’s disease, and developing GBA-targeting drugs, may be critical for PD patients.

The mechanisms underlying the effect of GBA mutations and glucocerebrosidase activity in PD are still not known. While GBA-specific drugs are already in different phases of development, they all follow the same pipeline of development as previous disease modifying drugs that have failed. For these reasons, G-QUEST (GBA Quebec Study Group) was established.


About the GBA-Quebec Study Group

G-QUEST is the first group of scientists and clinicians who are dedicated to solving the numerous challenges in GBA-PD research. Together, we aim to facilitate the development of GBA-targeting drugs into phase I clinical trials by:

  • Using different approaches than that typically used for drug development; and
  • testing new hypotheses; and
  • engaging the power of the Open Science collaborative approach.

G-QUEST is based on three pillars: (1) Basic science, (2) translational science and (3) clinical science. It includes experts in genetics, molecular biology, stem-cell research, physiology, brain imaging and network mapping, pathology, immunohistochemistry, lipid biology and lipidomics, structural biology, bid-data analysis, drug development, drug screening, clinical studies and clinical trials.

With a total of 13 principal investigators in its core group, a network of numerous collaborators, and built on the principles of Open Science, our team is best equipped to perform the most advanced and groundbreaking basic, translational, and clinical research in GBA-associated PD, and eventually all PD.   

The Neuro is the optimal place to house G-QUEST since it is an independent neurological institute with clinical departments, clinics, and research labs under the same roof, all aiming to research and treat neurological disorders. The Neuro is also the first Open Science institute and as such, has an integrated infrastructure, and the research and its resulting data can be accessed by researchers and industry.



G-QUEST will lead a coordinated effort to attack all the different issues related to GBA in Parkinson’s disease. More specifically:

Accelerate of GBA-specific drug development
Using the advantages of the iPSCs platform, the Quebec Parkinson’s Network, the C-BIG sample repository, and international collaboration, we will create a drug screening platform dedicated to GBA-specific drugs. These drugs will be screened on multiple neurons and organoids (“mini-brains”) derived from patients with various mutations in GBA or in the GBA pathway. In parallel, worm and zebrafish models will be used for validation screening. These tools will be available for other researchers, industry, and foundations to use.

Target known research gaps and novel hypotheses
Many research gaps still exist in GBA research. For example, we do not know why certain people with GBA mutation develop PD while others do not. We do not know how GBA mutations lead to alpha-synuclein accumulation and development of PD. The G-QUEST team will target these and many other gaps, using hypothesis free approaches (e.g. different omics methods), and hypothesis-based approaches.

Generate GBA trial-ready populations
In parallel to the efforts above, G-QUEST will prepare populations for future clinical trials by screening for GBA mutations, performing a comprehensive genetic analysis that will allow for stratification based on genetic background, and supporting databases that will include these patients. Both PD and prodromal PD (RBD and healthy GBA carriers) will be the target of this approach.


Potential Impact

About 10% of PD patients have GBA mutations, and many of those without GBA mutations, have reduced glucocerebrosidase activity. Therefore, the potential impact of our study is massive. By taking a multidisciplinary approach, and through The Neuro’s open science principles, our group will accelerate and greatly advance the field that will hopefully lead to the development of new neuroprotective treatment for PD.




G-QUEST Collaborators

The Neuro logo McGill logoMcGill University Health Centre logoKillam logo


The Neuro is a McGill research and teaching institute; delivering high quality patient care, as part of the Neuroscience Mission of the McGill University Health Centre. We are proud to be a Killam Institution, supported by the Killam Trusts.




Back to top