Hidden Genetic Variants in Middle East Populations Highlight Gaps in Parkinson's Disease Treatment

A major international study into Parkinson’s disease has revealed significant blind spots in meeting the needs of people in the Middle East, despite individuals from the region carrying a key genetic variant associated with the condition. Research conducted by the US National Institute on Ageing and the German Centre for Neurodegenerative Diseases examined the genetic risk of more than 100,000 people. The progressive brain disorder causes mobility problems, as well as difficulties with sleep, mental health, and other bodily functions.

Research published in The Lancet Neurology suggests the Middle East is under-served by gene-targeted therapy, and that screening may miss important risk signals in the region's populations. Among people of Middle Eastern ancestry, a causal variant in the LRRK2 gene appeared in 4.4 per cent of people with Parkinson's disease, more than double the overall study rate. They also showed the highest frequency of PRKN gene variants (1.3 per cent), a major driver of early-onset Parkinson's disease. Despite these anomalies, these variants are largely under-studied outside European cohorts, leading to calls for wider research into ageing-related diseases.

Dr Lara Lange, a study author and fellow at the National Institute on Ageing Laboratories of Neurogenetics, noted that some genetic variants act as risk factors, increasing a person's likelihood of developing the disease by up to five times compared with non-carriers. “Our research shows that nearly 12 per cent of Middle Eastern Parkinson’s patients harbour an identifiable and potentially actionable genetic variant, primarily in LRRK2 and GBA1, which are targeted by leading precision drugs globally,” Dr Lange told The National. “Yet almost all clinical trials for these treatments currently take place in North America and Europe. This presents an opportunity for Gulf medical hubs. By expanding local screening and hosting clinical trials, we can ensure these next-generation therapies are accessible and effective for Middle East populations.”

Parkinson's disease-related disability and deaths are on the rise globally, increasing from 3 million cases in 1990 to around 12 million in 2025. Whether Parkinson's actually manifests depends on a complex mix of underlying genetic factors, advancing age, lifestyle habits, and environmental exposures. The Middle East records an age-standardised prevalence of roughly 83 per 100,000 people with the disease, but those rates are constantly climbing due to ageing populations and lifestyle changes.

Dr Muhammad Ghatali, a neurologist at Mubadala Health, Dubai, explained that while Parkinson's disease is not completely preventable, understanding genetic susceptibility can enable earlier treatment. “Usually we diagnose patients clinically by checking their symptoms such as loss of smell, gait issues, or sleep behaviours, but if they come in younger than 50, then we focus on genetics,” he said. “The standard treatment has been levodopa (dopamine), which is still the cornerstone. However, we are now using an MR-guided focused ultrasound, which offers a one-off permanent treatment to resolve the tremors.”

Although genetic variants carry different levels of risk, many carriers of LRRK2 or GBA1 variants never develop Parkinson's disease. “Disease prevalence rises significantly with age, but these neurological disorders are being recognised and diagnosed earlier,” Dr Ghatali added. “We have a unique opportunity in the UAE to contribute to global Parkinson's research because of the highly diverse population here. It can provide an ideal system for investigating how genetic and biological factors influence disease risk and progression across differential ancestry.”

Beyond clinical research, broader public health efforts can help reduce disease burden across the Arabian Gulf. Earlier clinical detection, improved access to specialised care and symptomatic treatments, and lifestyle interventions like regular physical exercise can support long-term quality of life. However, new research at the University of Southern California suggests the activity’s context—whether for work or leisure—can make a difference in reducing the risk of dementia later in life. A meta-analysis of more than 4.2 million people found that leisure-time exercise such as walking, cycling, running, swimming, or playing sports was associated with a substantially lower risk of dementia. In contrast, physical activity performed as part of a job appeared to be linked with a higher risk of developing the condition.

Participants aged 45 to 93 across 30 countries were tracked for 10 years to analyse diagnoses of dementia, Alzheimer’s disease, and vascular dementia. Overall, those who engaged in higher levels of leisure-time physical activity had a 24 per cent lower risk of dementia than those who were least active, while occupational physical activity was associated with a 20 per cent higher risk.

Dr Khaled Al Saffar, a neurologist at Medcare Hospital in Al Safa, Dubai, stated there was growing evidence that a healthy lifestyle can help protect brain health and potentially reduce the risk of cognitive decline. “Regular physical activity is particularly important, as exercise supports cardiovascular health, circulation, and overall brain function,” he noted. “For Parkinson’s specifically, genetics is only one part of the picture. A family history or genetic susceptibility does not necessarily mean someone will develop the disease.”

Artificial intelligence is also assisting scientists in discovering new therapeutic uses for existing drugs approved by the FDA. By mining healthcare databases, researchers found a hidden benefit for the GSK-produced shingles vaccine, Shingrix, which showed a significant reduction in dementia risk of up to 33 per cent. “Treatment has moved beyond simply prescribing medication,” Dr Al Saffar concluded. “We now look at the person as a whole and consider movement, balance, speech, swallowing, sleep, mood, cognition, and quality of life.”