## Breadcrumb - [Home](/) - [Living with Parkinson's](/living-with-parkinsons) - [My PD Story](/living-with-parkinsons/stories) ## Breadcrumb - [Home](/) - [Living with Parkinson's](/living-with-parkinsons) - [My PD Story](/living-with-parkinsons/stories) # My PD Story ![Patrick Lewis, PhD headshot](/sites/default/files/styles/470x550/public/images/Patrick%20Lewis%2C%20PhD.png?h=c9aea1bc&itok=KtRtFzFc) Researchers ## Patrick Lewis, PhD ***2025 Trailblazer Award*** ### Investigating How the Puzzling *G2385R* *LRRK2* Mutation Leads to Parkinson’s While aging and environmental factors are the greatest contributors to developing Parkinson’s disease (PD), [Parkinson’s Foundation research](/advancing-research/our-research/pdgeneration/genetics-behind-pd "Current Findings from PD GENEration") has found that approximately 13% of people with Parkinson’s have a known genetic link to the disease. For those people, a small change in their DNA (a DNA variant) contributes to PD-associated cellular disruptions. Variants of the gene that create a protein called *[Leucine-Rich Repeat Kinase 2 (LRRK2)](/understanding-parkinsons/causes/genetics "Genetics & Parkinson's")* are found in 1-5% of all PD cases. [Significant progress](/living-with-parkinsons/stories/tatyana-bodrug "Tatyana Bodrug, PhD") is being made to understand how *LRRK2* variants lead to PD, but some variants are more complicated than others, leaving gaps in our scientific understanding. Patrick Lewis, PhD, recipient of a Parkinson’s Foundation Trailblazer Award, is devoting his research to one perplexing *LRRK2* variant called *G2385R*. This variant affects a different area of the *LRRK2* protein than other more well-studied variants. Interestingly, the effects of the *G2385R* variant on cell function may be the opposite of other *LRRK2* variants, raising questions about how it leads to PD. > ### Decoding Gene Variant Naming > > Scientists use a specific alphanumeric pattern to name genetic variants, which commonly goes letter-number-letter. The first letter and number refer to an amino acid — building blocks of proteins — at a specific position in a protein blueprint chain. The second letter refers to what the variant changes the original amino acid into, potentially affecting the function of the protein. For *G2385R* variants, the uncharged glycine (G) in the 2385th amino acid slot in the chain to build *LRRK2* becomes a charged arginine (R) instead. ![Patrick Lewis, PhD ](/sites/default/files/styles/380x361/public/images/Patrick%20Lewis%2C%20PhD%20working.png?itok=89mX_P5V) From his lab at the Royal Veterinary College in London, UK, Dr. Lewis is preparing a wide range of experiments to fully understand how *G2385R LRRK2* operates within cells and how it contributes to PD. First, he and his team will observe the biochemical activity of the variant protein, comparing and contrasting its functionality to both original *LRRK2* and other *LRRK2* variants. They will then monitor how the variant *LRRK2* reacts to biological stress within the cell, where it moves and accumulates and how that disrupts other pathways and processes. Finally, Dr. Lewis will test how various drugs, including LRRK2 inhibitors currently undergoing clinical trials, impact *G2385R LRRK2*, providing insight into potentially useful therapeutics in the future. The *G2385R LRRK2* variant is more common in east Asia than in Europe or America, affecting nearly 2% of people with PD across countries including China, Japan and Korea. Understanding the disease association of this variant will go a long way in advancing treatments not just for those hundreds of thousands of people with the *G2385R* variant, but for all those with *LRRK2* variants as our scientific understanding of the whole protein increases. When asked about what this support means to him and his work, Dr. Lewis said, “Receiving a Trailblazer Award from the Parkinson's Foundation is really an honor. This project will allow me to develop a new avenue of research investigating *LRRK2* to understand how one of the most common Parkinson's risk variants worldwide can increase the likelihood of developing Parkinson's at a functional level.” **Meet more Parkinson’s researchers! Explore our** [My PD Stories featuring PD researchers](/living-with-parkinsons/stories "My PD Story"). ## Related Materials Fact Sheets ### [ Getting Involved in Research ](/library/fact-sheets/research) [Read Now](/library/fact-sheets/research) Fact Sheets ### [ Genetics ](/library/fact-sheets/genetics) [Read Now](/library/fact-sheets/genetics) Books ### [ Women and Parkinson's Research and Care Agenda ](/library/books/women-research-care-agenda) [Read Now](/library/books/women-research-care-agenda) ## More Stories from the Parkinson's community ![Wilma van de Berg](/sites/default/files/styles/340x400/public/images/Wilma%20Van%20Berg%20Headshot.png?h=c9aea1bc&itok=h2_ydEqq) Researchers ### [ Wilma van de Berg ](/living-with-parkinsons/stories/wilma-van-de-berg) READ NOW ![Heba Deraz, MD, PhD Headshot](/sites/default/files/styles/340x400/public/images/Heba%20Deraz%2C%20MD%2C%20PhD.png?h=c9aea1bc&itok=1EZm7iUx) Researchers ### [ Heba Deraz, MD, PhD ](/living-with-parkinsons/stories/heba-deraz) READ NOW ![Paolo Moretti headshot](/sites/default/files/styles/340x400/public/images/Paolo%20Moretti.png?h=c9aea1bc&itok=buSEmwa_) Researchers ### [ Paolo Moretti, MD ](/living-with-parkinsons/stories/paolo-moretti) READ NOW [VIEW ALL STORIES](/living-with-parkinsons/stories) ### Share your Story Do you have an experience with Parkinson's that you would like to share? [SUBMIT YOUR STORY](/living-with-parkinsons/my-pd-story/submit) ### Join the PD GENEration Today PD GENEration is an initiative that offers genetic testing and genetic counseling at no cost for people with Parkinson’s disease. [ENROLL NOW](/advancing-research/our-research/pdgeneration) - Share on Facebook - Share on X - Share on LinkedIn