A review led by UCL researchers and published in The Lancet Neurology highlights growing evidence that changes in a gene called GBA1 play an important role in some cases of Parkinson’s. These genetic differences appear to influence how the condition develops and how severe it becomes. 

The review’s authors report that people with certain GBA1 gene variants tend to experience a slightly earlier onset and a faster progression of Parkinson’s symptoms, including more pronounced problems with thinking, movement, and the body’s automatic functions, such as blood pressure control.

Although these genetic variants increase risk, most people who carry them will not go on to develop Parkinson’s, highlighting that the condition still depends on a mix of genetic and environmental factors.

Parkinson’s has long been treated as a single disease, but the findings add to a growing shift in how scientists understand the condition. Instead of one condition, Parkinson’s may be a group of related diseases with different causes and outcomes. 

Understanding these differences could help doctors move away from a ‘one-size-fits-all’ approach to treatment and towards more personalised care for patients.

The GBA1 pathway is now being explored as a target for new treatments. Researchers are investigating therapies designed to correct or compensate for the changes caused by these gene variants, in the hope of slowing or even preventing disease progression. 

The review authors conclude that more research is necessary to understand the relationship between GBA1 variants and Parkinson’s. Only a small proportion of people with GBA1 variants ever develop Parkinson’s or a related condition called dementia with Lewy bodies. The understanding of the mechanisms that underlie conversion to Parkinson’s disease or dementia with Lewy bodies is needed, as it is also necessary to identify the prodromal features for those carriers most at risk.

Dr Elisa Menozzi (UCL Queen Square Institute of Neurology) said: “Our findings add to growing evidence that Parkinson’s disease is not a single condition, but a group of disorders with different underlying causes. By understanding how genetic factors such as GBA1 influence the disease, we move closer to more precise and personalised approaches to diagnosis and treatment.”

 

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