Young-Onset Parkinson’s on the rise in India: Genetic research paves way for early detection

synopsis

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Parkinson's disease (PD), a progressive neurological illness that is characterized by slowed movements, tremors, balance problems, and more, is the secondmost common neurodegenerative disorder in adults after Alzheimer’s disease. Over the past two decades, the burden of PD has doubled across the globe, with India accounting for approximately 10% of the global burden, which translates to over half a million patients living with the disease.

Parkinson’s Disease has traditionally been thought to be an old age disease occurring inlate 60s or 70s.However,it is now increasingly being diagnosed in younger adults, leading to concerns about Young-Onset Parkinson's Disease (YOPD) in India.YOPD is defined as PD that occurs before the age of 50 years.

While enhanced medical technologies available in the last few decades have contributed to the increased diagnosis of YOPD, it is often difficult to identify due to its vastly varied symptoms, necessitating highly skilled clinical practitioners for precise diagnosis.

Role of Genetic Factors:

25% of all Parkinson's disease have a genetic origin, with the other 75% being unknown. Family history for PD is an established risk factor, especially in first-degree relatives or second-degree blood relatives, referred to as Familial Parkinson’s Disease. A PD patient without a positive family history is defined as Sporadic Parkinson’s disease, which accounts for a majority of diagnosed PD cases. Genetics plays an important role in both these types of PD, whether it is an inherited genetic mutation or a non-inherited one.

• A rare pathogenic mutation in about 10 genes, including PRKN, LRRK2, GBA, SNCA, PINK1, etc., defines the monogenic genetic cause for PD.

• About 1700 common genetic variations that are associated with PD, which collectively confer the polygenic risk of development of the disease.

Recent research efforts in India have focused on characterizing the genetic landscape of YOPD within the South Asian population. These studies have identified genetic variations specific to the Indian population with YOPD and observed correlations between specific genetic mutations and distinct clinical presentations, potentially aiding in earlier and more accurate diagnosis.

For instance, one study identified the GBA mutation p.S164R loss-of-function for the first time reported in South Asian PD patients. Another study, a landmark research initiative by MedGenome, conducted in collaboration with the Parkinson Research Alliance of India (PRAI), found both rare and common genetic variations associated with YOPD, thus improving the understanding of the genetic basis of the disease.

These studies have also validated the use of polygenic risk scores (PRS) as a tool to assess genetic risk in the South Asian population. PRS considers the combined effect of multiple common genetic variants, offering a more comprehensive assessment of risk than focusing solely on single, high-impact mutations.

The insights gained from these research initiatives are contributing to the development of improved risk assessment strategies. Although there is no therapeutic option to cure PD at present, an early identification of the risk allows for proactive consultation with clinicians and implementation of lifestyle modifications to potentially mitigate the development of PD.

Young-Onset Parkinson's Disease is an emerging concern in India, demanding increased awareness and research. Ongoing research efforts are significantly advancing our understanding of the genetic underpinnings of YOPD in the Indian population. Continued research and collaboration are crucial to improve diagnostic accuracy, develop targeted therapies, and ultimately improve the lives of individuals affected by YOPD in India.

-By Dr Ramesh Menon, Associate Director of Personal Genomics and Genomic Medicine, MedGenome