Parkinson's disease in the Western Pacific Region

Lim, Shen Yang; Tan, Ai Huey; Ahmad‐Annuar, Azlina; Klein, Christine; Tan, Louis C.S.; Rosales, Raymond L.; Bhidayasiri, Roongroj; Wu, Yih Ru; Shang, Huifang; Evans, Andrew; Pal, Pramod Kumar; Hattori, Nobutaka; Tan, Chong Tin; Jeon, Beomseok; Tan, Eng King; Lang, Anthony E.

doi:10.1016/s1474-4422(19)30195-4

Cited by 140 publications

(142 citation statements)

References 109 publications

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“…Interestingly, low rates of dyskinesias and motor fluctuations have also been reported in Western Pacific countries [2]. Deeper knowledge in inter-ethnic genetic variations in postsynaptic dopamine maintenance could shed light on the biological basis of the observed low rates of levodopa complications in Asians [2]. Important to note, that mild levodopa complications, especially motor fluctuations, could have been underacknowledged by movement disorders specialists in Kazakhstan, and were not mentioned in the clinical records that this study reviewed.…”

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confidence: 81%

“…Considering the mean disease duration (7.1 ± 5.2) and the daily dose of levodopa of 500 mg and more in 58% of patients, one would expect higher rates of motor complications. Interestingly, low rates of dyskinesias and motor fluctuations have also been reported in Western Pacific countries [2]. Deeper knowledge in inter-ethnic genetic variations in postsynaptic dopamine maintenance could shed light on the biological basis of the observed low rates of levodopa complications in Asians [2].…”

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confidence: 96%

“…Little is known about Parkinson's disease (PD) epidemiology, demographics, genetics and clinical presentation in Central Asian countries. Western and East Asian studies have suggested that PD might have variable clinico-demographic characteristics in different ethnic groups [1][2][3]. In this regard, here we make a first demographic and clinical analysis of a large PD cohort in Kazakhstan, the biggest Central Asian country, residing between Europe and East Asia.…”

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confidence: 96%

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Parkinson’s Disease in Kazakhstan: Clinico-Demographic Description of a Large Cohort

Kaiyrzhanov

Zharkinbekova

Shashkin

et al. 2020

JPD

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confidence: 81%

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confidence: 96%

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confidence: 96%

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Parkinson’s Disease in Kazakhstan: Clinico-Demographic Description of a Large Cohort

Kaiyrzhanov

Zharkinbekova

Shashkin

et al. 2020

JPD

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“…For example, the G2019S mutation, which is common in Whites, confers a higher risk for PD than the common Asian variants, G2385R and R1628P [11,13]. These latter two variants are detected in around 5-10% of Asian PD patients [45]. The G2385R variant is associated with an odds ratio of 2.24.…”

Section: Lrrk2-associated Parkinsonism: Kinase Inhibitors Are a Promomentioning

confidence: 99%

Precision medicine in Parkinson’s disease: emerging treatments for genetic Parkinson’s disease

Schneider

Alcalay

2020

J Neurol

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In recent years, numerous clinical trials for disease modification in Parkinson's disease (PD) have failed, possibly because of a "one-size-fits all" approach. Alternatively, a precision medicine approach, which customises treatments based on patients' individual genotype, may help reach disease modification. Here, we review clinical trials that target genetic forms of PD, i.e., GBA-associated and LRRK2-associated PD. In summary, six ongoing studies which explicitely recruit GBA-PD patients, and two studies which recruit LRRK2-PD patients, were identified. Available data on mechanisms of action, study design, and challenges of therapeutic trials are discussed.

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“…Indeed, there is abundant literature showing that the most common LRRK2 mutation found in Caucasians, G2019S, results in augmented LRRK kinase activity [3,4]. However, this causative autosomal dominant mutation is exceedingly rare in all Asian PD populations studied so far [5,6]. Instead, "Asian LRRK2 risk variants" such as G2385R and/or R1628P, which are associated with approximately a 2-fold elevated risk of developing PD, are common and present in up to 5-10% of East Asian (Chinese, Japanese, Korean) patients [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Clinical Phenotype of LRRK2 R1441C in 2 Chinese Sisters

Lim

Ahmad‐Annuar

et al. 2020

Neurodegener Dis

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Pathogenic and risk variants in the LRRK2 gene are among the main genetic contributors to Parkinson’s disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK-LRRK2are now entering clinical trials. However, in contrast to the LRRK2 G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causative LRRK2 mutations, and data on genotype-phenotype correlations are largely lacking. This report is from an ongoing multicentre study in which next-generation sequencing-based PD gene panel testing has so far been conducted on 499 PD patients of various ethnicities from Malaysia. We describe 2 sisters of Chinese ancestry with PD who carry the R1441C mutation in LRRK2 (which in Asians has been reported in only 2 Chinese patients previously), and highlight interesting clinical observations made over a decade of close follow-up. We further explored the feasibility of using a brief, expert-administered rating scale (the Clinical Impression of Severity Index; CISI-PD) to capture data on global disease severity in a large (n = 820) unselected cohort of PD patients, including severely disabled individuals typically excluded from research studies. All patients in this study were managed and evaluated by the same PD neurologist, and these data were used to make broad comparisons between the monogenic PD cases versus the overall “real world” PD cohort. This report contributes to the scarce literature on R1441C PARK-LRRK2, offering insights into natural history and epidemiological aspects, and provides support for the application of a simple and reliable clinical tool that can improve the inclusion of under-represented patient groups in PD research.

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Parkinson's disease in the Western Pacific Region

Cited by 140 publications

References 109 publications

Parkinson’s Disease in Kazakhstan: Clinico-Demographic Description of a Large Cohort

Parkinson’s Disease in Kazakhstan: Clinico-Demographic Description of a Large Cohort

Precision medicine in Parkinson’s disease: emerging treatments for genetic Parkinson’s disease

Clinical Phenotype of <b><i>LRRK2</i></b> R1441C in 2 Chinese Sisters

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