MOVES-PD was a global Phase 2 study to assess the efficacy and safety of a drug called venglustat in Parkinson’s patients who have a GBA-1 genetic mutation. The pharmaceutical company Sanofi conducted the trial to determine if venglustat could change the course of the disease. When the final data was collected, however, the results of the study indicated that the drug had no impact on slowing the progression of the condition.  

Sanofi designed the MOVES-PD study, which involved 221 people with GBA-associated Parkinson’s being administered with either venglustat or a placebo treatment for one year, to determine if venglustat could improve performance of on clinical measures of disease progression (the Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Parts II and III). Unfortunately, Sanofi have announced that the clinical trial has not demonstrated any improvements.

Find out more about GBA-associated Parkinson’s

Glucocerebrosidase (also known as GCase) is an enzyme that helps to break down and recycle old proteins and waste  within cells. The enzyme is located inside lysosomes, which are small bags of digestive enzymes. Lysosomes represent an important component of the waste disposal system of cells, and disruption of lysosomal function has been associated with many types of neurodegenerative diseases. The GCase enzyme is made from instructions provided by a region of DNA called the GBA-1 gene.

Variations in the GBA-1 gene represent one of the most common genetic risk factors associated with Parkinson’s. Individuals who are diagnosed with Parkinson’s and also carry a GBA-1 variant in their DNA typically have an earlier onset of symptoms and a faster progressing form of the condition (although this can vary between cases). Researchers refer to this form of the condition as GBA-associated Parkinson’s, and given the assumed underlying involvement of the Glucocerebrosidase (GCase) enzyme, a lot of research is now focused on this molecule.

It is estimated that as many as seven to ten percent of people living with Parkinson’s carry at least one GBA-1 mutation.

Why is GBA-associated Parkinson’s such an important target?

If you have met one person with Parkinson’s, you have only met one form of this disease as each person presents with their own combination of symptoms.  Recently a better understanding of the genetics underlying some cases of Parkinson’s has pointed towards certain aspects of biology that can be targeted in our hunt for better treatment. It has also allowed us to propose different ‘sub-types’ of Parkinson’s that we may be better able to treat with new therapeutics.

GBA-associated Parkinson’s represents one of these potential sub-types of Parkinson’s, and numerous treatment approaches are now being tested on this group of the Parkinson’s community. If one of these novel therapies allows us to slow or halt the progression of GBA-associated Parkinson’s, it will provide proof that a targeted approach can be applied to the disease and encourage further research into other subtypes.

Read more about venglustat and Parkinson’s

Venglustat is a drug that has been developed to reduce the production of the molecule glucosylceramide that the Parkinson’s-associated GCase enzyme degrades. In extensive research in pre-clinical models of Parkinson’s, it was shown that venglustat decreased levels of glucosylceramide, resulting in less stress on nerve cells that had the GBA-1 genetic risk factor for Parkinson’s. The hypothesis was that by reducing excess glucosylceramide accumulation in cells, venglustat might prevent neurodegeneration and slow down the progression of the disease. After exhaustive preclinical research, it was decided to test venglustat in people with GBA-associated Parkinson’s.

Next steps:

Significant insights have been learnt from the MOVES-PD study and these will be taken forward to help with future trials in GBA-associated Parkinson’s. Sanofi has pledged to learn as much as it can from this study and share their findings with the Parkinson’s research community for the benefit of the field and to inform future studies.  They have planned to follow-up with participants over time and this data is crucial to better understand and explain the findings in more detail.

While the outcome of MOVES-PD was not what we had hoped, Sanofi remains committed to further analyses of the data and transparent communication with the Parkinson’s community.  The support of researchers and contribution of patients worldwide demonstrates a strong spirit of collaboration, and we will continue to honor this in our work.

Dr Pablo Sardi, R&D Director, Sanofi

Even though the venglustat trial has not been successful, the pipeline for GBA-associated Parkinson’s is rich with potential therapeutics targeting the GBA pathway, including:

Ambroxol, a repurposed drug, prioritised by Cure Parkinson’s International Linked Clinical Trials Committee (iLCT) in 2015 and commonly used in Europe as an anti-mucolytic respiratory medicine.

BIA 28-6156 is a GCase enzyme activator being developed by BIAL Biotech. After completing its Phase 1 safety clinical trial, it was prioritised by the iLCT committee in 2020 and will be moving into phase 2 trials in 2022.

PR001A is a gene therapy treatment being developed by Prevail Therapeutics. Gene therapy involves treating conditions with DNA rather than drugs, and the researchers are attempting to replace the faulty GBA-1 gene in the brains of people with GBA-associated Parkinson’s with a normal version of the gene. A five-year Phase 1/2a clinical trial is currently on-going in the U.S.


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