Research led by the Paris Brain Institute at the Sorbonne University shows that in some cases of Parkinson’s disease, the type of genetic mutations a person has could impact their disease prognosis.
In an analysis of different patients with the condition, the researchers found that some genetic mutations improved prognosis, while others worsened disease outlook for the patients compared with no mutations.
Parkinson’s disease is caused by loss of nerve cells in a part of the brain called the substantia nigra. However, the exact cause of this neurodegeneration is unclear in many cases. It is believed that a combination of genetics and environmental causes can trigger the condition, but triggers seem to vary between patients.
Around 5% of cases are thought to be caused by a single gene variant. A number of such variants and molecular drivers have been linked to Parkinson’s disease in some patients during previous research, but the impact they have on disease progression was not clear.
To investigate the impact of single gene variants on prognosis, Aymeric Lanore and colleagues from the Paris Brain Institute assessed whether a group of 2037 patients with Parkinson’s had mutations in the four most common genes linked with the condition— SNCA, LRRK2, PRKN, or GBA—and evaluated the impact on survival time following diagnosis.
Patients with mutations in LRRK2 or PRKN had 50-58% longer survival than those with the condition, but without a mutation in these genes. In contrast, SNCA or GBA mutations conveyed a 10.20- and 1.36-fold shorter survival time than individuals without any of these mutations.
“The results suggest the shorter survival of SNCA and GBA patients may be related to faster motor progression of the disease and earlier development of cognitive impairment,” explained Lanore, who presented the study at the European Academy of Neurology annual congress in Vienna, in a press statement. “These are important new insights which could help the development of new drugs targeting these genetic variants to slow down or stop the disease.”
While there are no immediate treatment changes that will be implemented as a result of this study, the team believes this information, if validated, will help clinicians advise patients better about their prognosis.
“These findings not only help increase our understanding of what drives the progression of Parkinson’s disease, but they may also enable clinicians to have honest conversations with their patients about expected survival times – just as cancer patients are told their prognosis. This can empower patients to make decisions about their care and the time they may have left,” concluded Lanore.
