Professor David Siu: precision medicine for hereditary diseases
The success of the research implies that scientists are one step closer to applying stem cells in precision medicine in treating patients suffering from various rare hereditary diseases.
Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in the environment, lifestyle, and genetic makeup of patients. Patient‐specific hiPSCs hold promise to transform precision medicine into real‐life clinical practice.
Lamin A/C-related dilated cardiomyopathy is a rare hereditary heart disease that affects about 100 people in Hong Kong. A substantial proportion of mutations in the Lamin A/C gene are of nonsense mutation. PTC124 induces translational read‐through over the premature stop codon and restores production of the full‐length proteins from the affected genes.
The research team, led by Prof David Chung-wah Siu (Croucher Fellowship 2005) of the University of Hong Kong, generated hiPSC‐derived cardiomyocytes from three patients with different LMNA mutations to evaluate the potential therapeutic effects of PTC124 in LMNA‐related cardiomyopathy.
Research method and significance
It was shown that these cells reproduced the pathophysiological hallmarks of LMNA-related cardiomyopathy. Interestingly, PTC124 treatment restored the gene function and reversed pathological process in 1 of the 3 mutant heart muscle cell lines. The PTC124 treatment did not work on stem cells of the two other families as their cells carried a slightly different type of genetic mutation, reflecting the drug's codon selective effect.
The study demonstrated the importance of precision medicine in predicting clinical responses of dilated cardiomyopathy patients and studying disease mechanisms.
“ With the hiPSC technology and in vitro drug testing strategies, scientists are one step closer to applying stem cells in precision medicine in treating patients suffering from various rare hereditary diseases.” said Siu, “We are now building up a library of disease-specific-hiPSC in order to facilitate research in understanding, treating, and preventing human diseases.”
The latest findings were published in the Journal of the American Heart Association.
Prof Chung Wah Siu currently works as Clinical Professor of the Department of Medicine at the University of Hong Kong. He obtained his medical degree (M.B., B.S.) in 1997 and Medical Doctor (M.D. with Sir Patrick Manson Gold Medal) in 2010 at the University of Hong Kong. Having completed a training program in Cardiology at Queen Mary Hospital, he commenced his career as a cardiologist in 2004. In the quest to improve treatment for patients with heart disease, he pursued study in Traditional Chinese Medicine concurrently at the Hong Kong Baptist University and Hubei College of Traditional Chinese Medicine, leading to the award of a Master degree in Traditional Chinese Medicine in 2005. Realizing the limitations of current clinical treatment for heart disease, he recognized the potential of stem cell therapy. With the Croucher research fellowship, he pursued his research career in the area of stem cell research at the University of California, Davis, USA from 2006-2007.
To view Prof Siu’s Croucher profile, please click here.