New MRI study to examine genetic underpinnings of Parkinson's disease

While the overall number of people affected by Parkinson’s disease (PD) in the world is exponentially rising, the cause of this chronic neurodegenerative disease is not yet clear. However, several factors are known to either protect or contribute to the development of Parkinson’s disease, among which we count a variety of environmental factors. Pesticides or a history of traumatic brain injury were identified as risk factors, whereas PD is rarer in individuals who smoke or have regular caffeine intake. Additionally, accumulating evidence shows that alterations of the genetic information (known as mutations) contribute to the susceptibility to Parkinson’s disease and explain around 20% of PD cases.

Today, the most important gene defining the risk to develop Parkinson’s disease in populations worldwide is the Glucocerebrosidase gene (GBA). This gene encodes the protein called beta-glucocerebrosidase – an important enzyme for the clearance of dysfunctional proteins from the cells. If the gene is mutated, cells cannot efficiently get rid of protein waste and finally degenerate. If a person carries two mutations in the GBA gene (in the copies inherited from the mother and the father), this translates into a childhood disorder called “Gaucher disease”. However, carrying only one mutation in the GBA gene represents a 30% probability of developing Parkinson’s disease during life. The occurrence of the GBA mutation does not automatically lead to the development of Parkinson's but constitutes the most important genetic risk factor.

For this reason, a new study within our National Centre for Excellence in Research on Parkinson’s disease (NCER-PD) was launched to define:

• the consequences of mutations in the GBA gene on the structure and function of the brain
• how one can differentiate between GBA mutation carriers with a risk of developing Parkinson’s disease and those who do not develop neurological symptoms.

Identifying early changes in the brain structure and function will help researchers identify carriers of GBA mutations that would profit from early neuroprotective treatments to prevent neurodegeneration leading to Parkinson’s disease. Currently, the first clinical trials are performed in Parkinson’s disease patients carrying mutations in the GBA gene to restore the impaired function of the encoded enzyme and slow down, or even stop, the premature ageing of cells underlying the chronic progressive disease (Ambroxol in Disease Modification in Parkinson’s Disease, Ambroxol as a Treatment for Parkinson’s Disease Dementia).