Genetic Mutation & Parkinson’s: Knowledge is Power

Much of our understanding of Parkinson’s disease (PD) comes from genetic studies. The most common genetic changes linked to PD occur in the GBA gene. People with PD who have a change (known as a mutation) in their GBA gene have been found to be more likely to experience 1) a younger onset of PD, 2) a more intense disease course, 3) an increased risk of dementia, and 4) tend to have a shorter life span than those with PD who do not have the GBA gene mutation.

The GBA gene, when functioning properly, provides instructions for toxic waste clean-up in a person’s cells. A GBA gene mutation may lead to a dangerous toxic build-up that can harm one’s brain, and other essential organs.

Did you know that our PD GENEration study offers free genetic testing to those with a Parkinson’s diagnosis?

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Having a GBA gene mutation has been identified in upwards of 12% of PD cases of people from European descent and 15-20% of Ashkenazi Jewish cases. Despite how common this mutation is, there have been surprisingly few good studies comparing the motor and functional decline of those with and without the GBA gene mutation — particularly from early diagnosis. Fortunately, a just-published, seven-year study that followed a group of people with Parkinson’s over time, sought to tackle this important shortcoming.

A study titled, “Association of GBA Genotype with Motor and Functional Decline in Newly Diagnosed Patients with Parkinson’s Disease” (Maple-Grodem et al., 2021), drew from three large European population-based PD studies (the Norwegian ParkWest, the Swedish NYPUM, and the Scottish PINE). Participants in this study included 53 GBA mutation carriers (in their mid-50s to mid-70s; 64% male) and 387 without the GBA gene mutation (in their early 60s to their late 70s; 60% male). Then, each year for seven years, the study participants’ motor and functional impairments (difficulties in performing activities of daily living) were meticulously evaluated using well-established PD scales, along with other sophisticated models and tests. Researchers took into consideration age, sex and duration of motor symptoms for each participant.

Results

At time of initial diagnosis:

Participants with and without the GBA mutation did not differ in overall motor severity or activities to perform (or complete) activities of daily living, nor in severity of tremor, rigidity, bradykinesia or trouble with balance.
GBA mutation carriers experienced their first motor signs of PD at an earlier age than non-carriers.
GBA mutation carriers were younger than non-carriers when initially diagnosed with PD.

Effects after seven years:

GBA mutation carriers had a more rapid motor decline than non-carriers.
There was statistically significant worsening in both the PD rating scores for GBA carriers compared to non-carriers — mostly driven by a steep decline in their bradykinesia and rigidity scores.

What Does It Mean?

This study investigated how having a GBA mutation impacts the motor and functional decline of people with PD over time. In brief, study participants with a GBA mutation experienced their first symptoms younger and were also diagnosed at a younger age than participants without this mutation. Of note, at the time of initial diagnosis, there was no distinguishable difference in the level of motor and function decline between GBA carriers and non-carriers.

Why is this study important? The speed of motor and function decline experienced by participants with a GBA mutation was faster compared to people without the genetic mutation. Such a profound decline impacts everything — from one’s independence to caregiver responsibility, and more. Having a better understanding — and armed with a reasonable predictability of PD progression — is essential for coordinating optimal health care for a significant proportion of the PD population. Better understanding these PD-related gene mutations and how they are linked to symptoms can help revolutionize PD research and future treatments.

While the study authors did not specifically advocate for genetic testing to become standard practice, they did suggest that knowledge of whether study participants are GBA mutation carriers would be valuable information, in terms of designing clinical trials and for interpreting the implications and applicability of study results.

Genetic studies, such as PD GENEration, help arm people with Parkinson’s with the knowledge of their genetic mutations, which can help them qualify for enrollment in more specialized clinical trials that are currently testing and optimizing PD treatments and medications that respond to particular genetic mutations.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about Parkinson’s and genetics by visiting the Parkinson’s Foundation resources below, or by calling our free Helpline at 1-800-4PD-INFO (473-4636) for answers to your Parkinson’s questions.