Stem Cells and Regenerative Medicine in the Treatment of Huntington's Disease Sarah Mohamed, Ramya M.
Department of Biotechnology, School of Applied Sciences, REVA University AIMS & OBJECTIVES
To highlight what is Huntington’s disease in brief. To discuss stem cell therapy and regenerative medicine for Huntington's Disease. ABSTRACT Huntington’s disease is a progressive neurodegenerative disorder inherited as an autosomaldominant trait, with onset typically occurring in mid-adult life and characterized by CAG trinucleotide repeat expansion in the Huntington (HTT) gene, which encodes Huntington protein (HTT). As Huntington's disease is a rare disease, pharmacological approaches targeting multiple domains of intracellular functions have been limited with respect to unwanted and harmful side effects. With more studies of the disease at a molecular level, recent developments in gene therapy, including stem cell therapy and regenerative medicine, are being explored for the Huntington’s community. In this poster, the current studies and the future outcome of the same is discussed. Keywords: Huntington's Disease; Treatment; Stem Cell Therapy, Regenerative Medicine; CAG repeats
HOW
WHAT • A progressive neurodegenerative disease
• CAG repeat expansions in the HTT gene, that codes the Huntington protein
WHERE
WHEN • Mid-Adult life
• Caudate nucleus and putamen of basal ganglia in the brain
INHERITANCE PATTERN • Autosomal dominant
Summary & Conclusion
Sources of Stem Cells
Fetal neural Stem cells
Fetal Neuronal proginator cells
Embryonic neuronal proginator stem cells
Non neuronal stem cells
Induced Pluripotent Stem Cells (iPSCs)
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• The aim of Stem Cell therapy is to replace the medium spiny projection neurons with functional neurons using cells from various sources • This method of treatment is currently tested in large and small model organisms and the results are being documented for future clinical trails. • With respected to pre-clinical transplantation done in transgenic mice models: • relatively effective electrophysiological and neurochemical improvement was seen • the transplanted cells connected and functioned properly with the host brain • Induced Pluripotent Stem Cells from the skin fibroblasts of Huntington Disease patients can be used in place of embryonic or fetal stem cells due to ethical issues •
MATERIALS AND METHODOLOGY •
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The Huntington's Disease community stands on the threshold of discovering highly targeted therapies that may reduce cell death caused by the toxic gain of function attributed to the mutated HTT gene. Stem Cell Therapy uses cells from embryonic or fetal striated tissues, neural stem cells, mesenchymal stem cells and induced pluripotent stem cells (iPSCs) in the treatment of Huntington's disease. Current research has been done using these cells in Huntington Disease mice models and point towards possible clinical trials. The clinical trials in which fetal striatal cells were used showed variable treatment outcomes A major challenge in Stem cell therapy for Huntington's is to produce a controlled differentiation of iPSCs and embryonic stem cells into specific neuronal phenotypes. A future approach of stem cell therapy is the development of neuronal regenerative medicine without ectopic side effects. Novel approaches to provide therapeutic molecules for neuro-protection are also under research. Hence, the future prospects can be to combine these molecular techniques with nano-delivery systems as successful therapies for Huntington Disease. REFERENCES •
PubMed-Medline, Elsevier, Springer databases were searched using Google Scholar to find research and review articles investigating the therapies of Huntington's Disease.
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The literature published from 2010 until 2020 was reviewed
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Shannon, K. M. (2020). Recent Advances in the Treatment of Huntington’s Disease: Targeting DNA and RNA. CNS drugs, 34(3), 219-228. Wild, E. J., & Tabrizi, S. J. (2017). Therapies targeting DNA and RNA in Huntington's disease. The Lancet Neurology, 16(10), 837-847. Tabrizi, S. J., Ghosh, R., & Leavitt, B. R. (2019). Huntington lowering strategies for disease modification in Huntington’s disease. Neuron, 101(5), 801-819. Tabrizi, S. J., Leavitt, B. R., Landwehrmeyer, G. B., Wild, E. J., Saft, C., Barker, R. A., ... & Rosser, A. (2019). Targeting Huntington expression in patients with Huntington’s disease. New England Journal of Medicine, 380(24), 2307-2316.