Croucher Symposium on Stem Cells and Neurological Diseases

From stem cells to exosomes and gene-targeted therapies: a translational journey in Huntington’s disease from Korea

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Abstract:

Huntington’s disease (HD) provides a unique framework for translational neuroscience: its genetic cause is well defined, yet effective disease-modifying therapy remains an unmet need. Over the past two decades, our research has explored how stem-cell biology can be translated into experimental therapeutic strategies for HD, progressing from cell replacement toward paracrine and cell-free approaches.

We established complementary HD models spanning mutant huntingtin-expressing cellular systems, patient-derived cells, and transgenic animal models. Early studies using adipose-derived stem cells demonstrated beneficial effects in HD models and suggested that therapeutic activity was not explained solely by cellular engraftment. This led us to investigate stem-cell-derived soluble factors and extracellular vesicles. Adipose stem-cell-derived exosomes ameliorated HD phenotypes in vitro, while subsequent studies implicated exosomes as biologically active mediators capable of modifying disease-related pathways.

More recently, we investigated human induced pluripotent stem cell-derived exosomes (iPSC-exo) as a cell-free therapeutic platform. In HD neural stem-cell models, iPSC-exo reduced mutant huntingtin aggregation and improved mitochondrial function, neuronal maturation and synaptic markers, while modulating apoptotic, inflammatory, and cell-survival pathways. These findings support a conceptual transition from cell replacement to cell-derived therapeutic signaling in HD.

HD has historically been considered uncommon and remains under-recognized in many Asian populations. Experience in Korea, including increasing disease awareness, patient networks, cohort development, and participation in emerging disease-modifying clinical trials, suggests that the burden and therapeutic needs of HD in the Asia-Pacific region deserve greater attention. Integrating disease modeling, regenerative biology, biomarkers, patient cohorts, and gene-targeted clinical therapeutics may provide a framework for accelerating HD research across Asia.

The Korean experience illustrates how sustained translational research can connect laboratory models with patients—and how Asian HD research can increasingly contribute to the global development of disease-modifying therapies.
 

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Biography:

Manho Kim, MD, PhD, is Professor of Neurology at Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Korea. He trained in neurology at Seoul National University Hospital and subsequently undertook postdoctoral training at Massachusetts General Hospital/Harvard Medical School.

For more than three decades, his research has focused on Huntington’s disease (HD), spanning molecular diagnosis, disease mechanisms, experimental models, stem-cell biology, regenerative therapeutics, and clinical studies. His laboratory has investigated stem-cell-based approaches to HD using cellular and transgenic models and subsequently explored paracrine mechanisms, stem-cell-derived cellular components, and extracellular vesicles. This work has progressed from adipose-derived stem cells and exosomes to recent studies of human iPSC-derived exosomes as a cell-free therapeutic strategy targeting mutant huntingtin-associated mitochondrial, synaptic, inflammatory, and apoptotic dysfunction.

Professor Kim has also contributed to the development of HD clinical and research networks in Korea and currently serves as President of the Korean Huntington’s Disease Study Group. His current interests focus on bridging experimental therapeutics, patient cohorts, and emerging disease-modifying and gene-targeted therapies for HD, with particular interest in advancing collaborative HD research across the Asia-Pacific region.