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National Library of Medicine

Polygenic Risk Score for Parkinson’s Disease in a South African Cohort

by Omar El Sayed - World Editor March 10, 2026

written by Omar El Sayed - World Editor

Cape Town, South Africa – A new study is offering a crucial step forward in understanding Parkinson’s disease (PD) risk, particularly within historically underrepresented populations. Researchers have, for the first time, evaluated the performance of polygenic risk scores (PRSs) – a tool for estimating an individual’s genetic predisposition to a disease – in a highly admixed South African cohort. The findings, published March 9, 2026, in PLoS Genetics, underscore the importance of diversifying genetic research to improve precision medicine for all.

Parkinson’s disease, a progressive neurodegenerative disorder affecting movement, is influenced by a complex interplay of genetic and environmental factors. While significant progress has been made in identifying genetic variants associated with PD, the vast majority of this research has focused on individuals of European ancestry. This creates a significant gap in knowledge regarding how genetic risk translates across different populations, limiting the effectiveness of predictive tools for those with diverse genetic backgrounds. The study addresses this critical need by examining PRS performance in a South African population, which exhibits a unique and complex genetic history.

Evaluating Genetic Risk in a Diverse Cohort

The research team, led by Kathryn Step at Stellenbosch University, analyzed genotyping data from 661 individuals with Parkinson’s disease and 737 control subjects. They utilized a method called PRSice-2 to calculate polygenic risk scores, leveraging summary statistics from existing PD association studies as a baseline. The cohort was divided into training and validation groups to rigorously assess the predictive accuracy of the scores. Researchers tested various statistical parameters to optimize the PRS model for this specific population. According to the study, age at recruitment emerged as the strongest individual predictor of PD risk, while sex contributed the least.

The study revealed modest predictive performance, with an area under the curve (AUC) ranging from 0.5847 to 0.6183. While not a definitive diagnostic tool, these results represent a crucial first step in refining genetic risk prediction for Parkinson’s disease in admixed populations. The researchers emphasize that ancestry composition and study design significantly impact risk estimation in diverse groups, highlighting the need for tailored approaches.

The Importance of Ancestry in Genetic Research

The findings underscore a growing recognition within the scientific community that genetic risk factors can vary significantly across different ancestral groups. Traditional genetic studies, often relying heavily on European populations, may not accurately reflect the genetic architecture of disease in other populations. This can lead to inaccurate risk assessments and potentially limit the effectiveness of personalized medicine strategies. The South African cohort’s unique genetic makeup, resulting from centuries of migration and admixture, provides a valuable opportunity to address these disparities.

The research team notes that the study’s findings contribute to ongoing efforts to ensure that advances in precision medicine are globally relevant. By systematically assessing predictive performance across different datasets, they aim to refine genomic prediction models and improve risk stratification for individuals from diverse backgrounds. The study also highlights the need for increased representation of underrepresented populations in genetic research initiatives.

Future Directions and Implications

This research lays the groundwork for future studies aimed at refining genomic prediction in admixed populations. Further investigation is needed to identify specific genetic variants that contribute to PD risk in the South African context and to develop more accurate and personalized risk assessment tools. Researchers are also exploring the potential of incorporating environmental factors and gene-environment interactions into PRS models to improve predictive accuracy. The National Institutes of Health’s Center for Alzheimer’s and Related Dementias, a collaborating institution in this study, continues to support research into the genetic basis of neurodegenerative diseases, including Parkinson’s. Further research is being conducted on the co-option of Rubisco small subunit by potyvirids.

The study’s authors acknowledge a conflict of interest: I.F.M. Has received honorarium from the Parkinson’s Foundation PD GENEration Steering Committee and Aligning Science Across Parkinson’s Global Parkinson Genetic Program (ASAP-GP2).

This research represents a significant step towards a more equitable and inclusive approach to genetic research and precision medicine. As our understanding of the genetic basis of Parkinson’s disease continues to evolve, it is crucial to prioritize diversity and ensure that the benefits of scientific advancements are accessible to all populations.

What are your thoughts on the importance of diverse representation in genetic research? Share your comments below, and assist us spread awareness about this critical issue.

Disclaimer: This article provides informational content and should not be considered medical advice. Please consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.

March 10, 2026 0 comments

world

Magnetofluid LAAO: Personalized, Thrombus-Free Left Atrial Appendage Occlusion

by Omar El Sayed - World Editor March 5, 2026

written by Omar El Sayed - World Editor

Innovative Approach to Left Atrial Appendage Occlusion

Researchers have introduced a groundbreaking method for long-term thrombus-free left atrial appendage occlusion (LAAO) utilizing magnetofluids. This new technique addresses significant challenges faced by current LAAO methods, primarily peri-device leaks and device-related thrombus, which arise from the incompatibility between traditional solid occluders and the left atrial appendage (LAA).

The innovative approach allows magnetofluids to be injected into the LAA via cardiac catheters, where they can effectively resist high-speed blood flow under a magnetic field. This process transforms the magnetofluids into magnetogels upon contact with blood, potentially offering a more efficient and safer alternative for patients at risk of thromboembolic events.

Study Highlights and Key Findings

A recent study demonstrated the efficacy and safety of this method over a 10-month period in a pig model. Notably, researchers found:

No device-related thrombi or leakage of magnetogel occurred in any of the test subjects.
The endocardium formed around the magnetogel was smooth and firm, in contrast to the rough, incomplete endocardium associated with existing occluders like the Watchman device.
No myocardial injuries were observed, highlighting the biocompatibility of the magnetogel compared to the barbed design of other devices.

Clinical Implications and Future Prospects

This novel LAAO technique presents significant clinical implications, particularly for patients with atrial fibrillation who are at high risk for stroke. The absence of thrombus formation and the reduction of myocardial injury could improve patient outcomes and expand the use of LAAO in clinical practice.

With the promising results from animal studies, the next steps will involve transitioning to human trials. If successful, this approach could redefine the standard of care for LAAO, potentially leading to wider acceptance and application in cardiovascular medicine.

Conclusion

The introduction of magnetofluids for left atrial appendage occlusion represents a pioneering advancement in cardiology, addressing critical issues of safety, and efficacy. As researchers prepare for human trials, the medical community eagerly anticipates the potential impact of this innovative method on patient care and outcomes in the field of cardiovascular health.

For more detailed information about this study and its findings, please visit Nature.

March 5, 2026 0 comments

Health

VV116 Pharmacokinetics & Safety in Mild/Moderate Hepatic Impairment – COVID-19 Treatment

by Dr. Priya Deshmukh - Senior Editor, Health February 25, 2026

written by Dr. Priya Deshmukh - Senior Editor, Health

The ongoing search for effective oral treatments for COVID-19 has yielded promising results for VV116 (Mindvy, JT001), a deuterated oral derivative of remdesivir hydrobromide. A recent Phase 1 study investigated how well the drug is processed by the body – its pharmacokinetics – and its safety profile in individuals with varying degrees of liver function. The findings, which could streamline treatment protocols, suggest that dose adjustments may not be necessary for patients with mild or moderate hepatic impairment.

Hepatic impairment, or reduced liver function, can significantly alter how the body metabolizes medications. Understanding these changes is crucial for ensuring drug efficacy and minimizing potential side effects. This study specifically addressed the impact of mild to moderate liver dysfunction on VV116, a drug designed to combat the SARS-CoV-2 virus. The research team aimed to determine if compromised liver function affected the drug’s absorption, distribution, metabolism, and excretion – key factors in its overall performance.

The Phase 1, open-label study involved adults with mild or moderate hepatic impairment, categorized using the Child-Pugh method, and a control group of healthy individuals. Each participant received a single 0.3-gram dose of VV116 while fasting. Researchers then meticulously collected blood samples over 72 hours to measure the concentrations of VV116 and its active metabolite, 116-N1, using a validated LC-MS/MS technique. The analysis focused on key pharmacokinetic parameters, including area under the curve (AUC), which reflects overall drug exposure; time to maximum concentration (Tmax); and half-life (t1/2), indicating how long the drug remains active in the body.

The results indicated that overall drug exposure (AUC) in participants with mild and moderate hepatic impairment was comparable to that of healthy controls, with geometric mean ratios (GMRs) of 94.10% (90% confidence interval [CI] 71.59%-123.68%) and 97.72% (74.34%-128.44%), respectively. Median Tmax and t1/2 were also similar across all groups. While the maximum drug concentration (Cmax) was slightly lower in those with liver impairment, the difference wasn’t considered clinically significant. This suggests that the liver’s ability to process the drug doesn’t drastically alter its overall impact on the body. Further research into VV116’s efficacy is ongoing, as detailed in a study published in The Lancet.

Safety and Tolerability

The study also assessed the safety and tolerability of VV116. Treatment-emergent adverse events were observed in 12.5% of participants with mild hepatic impairment, 37.5% of those with moderate impairment, and 12.5% of the control group. Importantly, all reported events were mild or moderate in severity, transient, and resolved without any intervention. The higher incidence of adverse events in the moderate impairment group was not deemed clinically meaningful, as these events were isolated and not linked to VV116 exposure levels. Notably, no serious adverse events, deaths, or study discontinuations occurred during the trial.

Researchers concluded that hepatic impairment did not have a clinically relevant effect on the pharmacokinetics of VV116. This finding supports the possibility that dose adjustments may not be necessary for patients with mild or moderate liver impairment, simplifying treatment protocols and potentially broadening access to this antiviral medication. The development of VV116 builds upon earlier work with remdesivir, as highlighted in research published in Nature detailing the design and development of this oral derivative.

Implications for COVID-19 Treatment

The availability of oral antiviral treatments remains a critical component of the global strategy to manage COVID-19. VV116, as an oral derivative of remdesivir, offers a potentially convenient alternative to intravenous administration. The current findings add to the growing body of evidence supporting its safety and efficacy. A recent comparison of VV116 to Nirmatrelvir–Ritonavir, another oral COVID-19 treatment, is available in The New England Journal of Medicine.

While this Phase 1 study provides valuable insights, further research is needed to confirm these findings in larger and more diverse populations. Ongoing clinical trials will continue to evaluate the long-term safety and effectiveness of VV116 in various patient subgroups, including those with more severe liver disease. A case report published in Frontiers also details dose determination in patients with severe liver dysfunction, adding to the growing understanding of this drug’s use.

The development of VV116 represents a significant step forward in the fight against COVID-19, offering a potentially accessible and well-tolerated treatment option for individuals with varying degrees of liver function. As research progresses, we can expect a more refined understanding of its role in managing this ongoing public health challenge.

Disclaimer: The information provided in this article is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.

What are your thoughts on the potential impact of oral antivirals like VV116 on managing COVID-19? Share your comments below.

February 25, 2026 0 comments

Health

ETI & Cystic Fibrosis Liver Disease: Impact on Liver Enzymes & Function

by Dr. Priya Deshmukh - Senior Editor, Health February 21, 2026

written by Dr. Priya Deshmukh - Senior Editor, Health

Cystic fibrosis (CF) is a genetic disease primarily affecting the lungs and digestive system, but its impact extends to other organs, including the liver. Recent advancements in treatment, particularly with the drug combination elexacaftor-tezacaftor-ivacaftor (ETI), have dramatically improved lung function and growth for many individuals with CF. Now, research is focusing on whether these benefits extend to mitigating liver complications associated with the disease. A new retrospective cohort study suggests that earlier employ of ETI may be linked to improved liver enzyme levels in children and young adults with CF.

The study, utilizing data from a large, de-identified database, investigated biochemical markers of cystic fibrosis-associated hepatobiliary involvement (CFHBI). Researchers aimed to determine if ETI, a modulator therapy targeting the underlying cause of CF, could positively influence liver health in patients. Understanding this connection is crucial, as liver disease is a significant cause of morbidity and mortality in individuals with CF. The findings offer a promising signal regarding the broader benefits of this newer treatment approach.

Study Design and Patient Population

Researchers conducted a 1:1 retrospective cohort study using the TriNetX database, a platform containing de-identified patient data from multiple healthcare organizations. The study included individuals aged 6 to 21 years diagnosed with cystic fibrosis, as indicated by ICD-10 diagnostic codes and who were prescribed pancreatic enzyme replacement therapy. Two groups were analyzed: a group receiving ETI (patients seen between January 1, 2020, and January 1, 2024) and a control group not receiving ETI (patients seen between January 1, 2014, and January 1, 2018). To ensure comparability, the groups were matched using propensity scores, a statistical technique used to balance potential confounding factors. Statistical analyses were performed directly within the TriNetX environment, with a significance level set at p = 0.05.

Key Findings: Improved Liver Enzymes with ETI

The study included 533 children with CF aged 6-12 years and 1177 adolescents and young adults aged 13-21 years in each cohort. In the younger children (6-12 years), those treated with ETI demonstrated significantly lower levels of alanine aminotransferase (ALT) – 33 ± 44 U/L compared to 45 ± 57 U/L in the non-ETI group (p = 0.003) – and gamma-glutamyl transferase (GGT) – 18 ± 20 U/L versus 28 ± 51 U/L (p = 0.004). Improvements were also observed in albumin and prothrombin time/international normalized ratio (PT/INR) in the ETI group. Among adolescents and young adults (13-21 years), the ETI group again showed significantly lower GGT levels (21 ± 26 U/L vs. 32 ± 63 U/L, p = 0.002) and improved albumin and PT compared to the non-ETI group. However, a notable difference emerged: indirect bilirubin levels were higher in the ETI group (0.7 ± 0.5 mg/dL vs. 0.3 ± 0.4 mg/dL, p < 0.001).

Implications and Future Research

These findings suggest that initiating ETI treatment earlier in children with CF may be associated with improvements in key liver enzyme markers, offering reassurance regarding the risk of widespread drug-induced liver injury. The researchers emphasize the need for continued, long-term follow-up, including imaging and, when available, liver biopsies, both before and after ETI initiation, to comprehensively assess the drug’s impact on CFHBI and the progression of advanced CF liver disease. Further investigation is needed to understand the clinical significance of the observed increase in indirect bilirubin levels in the older age group.

The study highlights the evolving understanding of CF and the potential for modulator therapies like ETI to address multiple organ system manifestations of the disease. While the initial focus of these therapies was on improving lung function, emerging evidence suggests a broader range of benefits. Continued research will be critical to optimizing treatment strategies and improving the long-term health outcomes for individuals living with cystic fibrosis.

Disclaimer: This article provides informational content and should not be considered medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment of any medical condition.

Have you or a loved one been affected by cystic fibrosis? Share your experiences and thoughts in the comments below.

February 21, 2026 0 comments

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