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Shen-Yang LIM, MD

University of Malaya

Kuala Lumpur, Malaysia

Working Groups

Area of Focus

  • Parkinson's disease
  • Parkinson's Plus Syndrome

Biography

Dr. Lim is a Senior Consultant Neurologist and Professor at the University of Malaya, Kuala Lumpur, Malaysia, where he runs a busy clinical practice specializing in Parkinson’s and related disorders.

Dr. Lim has published extensively in these areas, in major scientific journals, including 1st-author publications in Lancet Neurology, Movement Disorders, NPJ PD, etc.

He has been an active member of the International Parkinson & Movement Disorder Society (MDS), being closely involved in multiple task forces and committees. He is currently Chair of the MDS Asian-Oceanian Section (AOS).

Dr. Lim’s main research interests are in the following areas: (i) PD (particularly genetics and genotype-phenotype correlations; evidence-based medicine/clinical trials; non-motor features including gastrointestinal aspects; comorbidities; rating scales/disease staging; and patient-centred care); (ii) Parkinson-plus syndromes and other miscellaneous/”orphan” movement disorders, including progressive supranuclear palsy (PSP).

Weblink: https://umexpert.um.edu.my/limshenyang.html

Contact

[email protected]

Outputs and publications by Shen-Yang LIM, MD

Clinical and functional evidence for the pathogenicity of the LRRK2 p.Arg1067Gln variant
LRRK2-related Parkinson’s disease (LRRK2-PD) is the most frequent form of monogenic PD worldwide, with important therapeutic opportunities, exemplified by the advancement in LRRK2 kinase inhibition studies/trials. However, many LRRK2 variants, especially those found in underrepresented populations, remain classified as variants of uncertain significance (VUS). Leveraging on Malaysian, Singaporean, and mainland Chinese PD datasets (n=4,901), we describe 12 Chinese-ancestry patients harbouring the LRRK2 p.Arg1067Gln variant, more than doubling the number of previously reported cases (total n=23, 87% East Asian, mean age of onset:53.9years). We determine that this variant is enriched in East Asian PD patients compared to population controls (OR=8.0, 95%CI:3.0-20.9), and provide supportive data for its co-segregation with PD, albeit with incomplete penetrance. Utilizing established experimental workflows, this variant showed increased LRRK2 kinase activity, by ~2-fold compared to wildtype and higher than the European p.Gly2019Ser variant. Taken together, p.Arg1067Gln should be reclassified from a VUS to pathogenic for causing LRRK2-PD.
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Uncovering the genetic basis of Parkinson's disease globally: from discoveries to the clinic
Knowledge on the genetic basis of Parkinson's disease has grown tremendously since the discovery of the first monogenic form, caused by a mutation in α-synuclein, and with the subsequent identification of multiple other causative genes and associated loci. Genetic studies provide insights into the phenotypic heterogeneity and global distribution of Parkinson's disease. By shedding light on the underlying biological mechanisms, genetics facilitates the identification of new biomarkers and therapeutic targets. Several clinical trials of genetics-informed therapies are ongoing or imminent. International programmes in populations who have been under-represented in Parkinson's disease genetics research are fostering collaboration and capacity-building, and have already generated novel findings. Many challenges remain for genetics research in these populations, but addressing them provides opportunities to obtain a more complete and equitable understanding of Parkinson's disease globally. These advances facilitate the integration of genetics into the clinic, to improve patient management and personalised medicine.
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Underrepresented Populations in Parkinson's Genetics Research: Current Landscape and Future Directions
Research on Parkinson's disease genetics has lacked diversity, with a focus on European populations. A systematic review reveals imbalances, with limited studies on underrepresented populations.
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