Mesenchimal Stem Cells Transplantation: A promising treatment for Huntington’s Disease

Huntington's disease (HD) is a progressive neurodegenerative disorder which is caused due to repetitive CAG or glutamine expression along the coding region of the Huntington gene. This disease results in certain movement abnormalities, affective disturbances, dementia and cognitive impairments. To this date, there is no proper cure for this rare and fatal neurological condition but there have been certain advancements in the field of genetic animal model research studies to elucidate the understanding of the pathogenesis of this condition. Currently, HD follows a certain therapeutic approach which just relieves the symptoms but doesn't cure the underlying cause of the disease. Stem cell therapy can be a breakthrough in developing a potential cure for this condition.

#Neurodegenerativediseases?are a process of deterioration in the intellectual and cognitive function of the?#centralnervoussystem?due to chronic progressive loss of structure?[1]. Those diseases are responsible for contributing to about 6.3% of all diseases?[2]. Neurodegenerative diseases such as Alzheimer's disease (AD),?#Parkinson'sdisease?(PD),?#amyotrophiclateralsclerosis?(ALS), and?#Huntington'sdisease?is generally observable in the elderly population. But the causes associated with such degradation are poorly understood. When there is no available pharmacological treatment that offers long-term efficacy, recent progress in stem cell research shows great promise for the field. Human embryonic-derived stem cells and?induced pluripotent stem cells, specifically recent advances in multipotent?#adultstemcells, are helping to design therapeutics for those diseases and replace lost?#motorneurons?through autologous?#celltransplantation?[3].

Cells that can reiterate them continuously and differentiate themselves into various cell types are known as stem cells. There are two types of mammalian stem cells?#embryonicstemcells?(ESCs), and?adult stem cells?(ASCs) found in different adult tissues.?ASCs are undifferentiated non-reproductive cells derived from specific differentiated tissues in human bodies. As ASCs are non-reproductive cells, it is also known as somatic stem cell. There are a few types of ASCs; among them,?#MesenchymalStemCells?(MSCs) and Neural Stem Cells (NSCs) are used in different therapeutic applications. iPSCs are derived in the laboratory in a medium between ESCs and ASCs.?

Conventional therapies are given for the ease of symptoms [4]. These are not effective for an extended period and don't respond well to every patient. For the lack of proper therapeutic, cell-based approaches have emerging potential for designing therapeutic strategies to modulate?#neuropathology?that can modify disease age of onset or disease course. Several stem cells therapies have gained approval for clinical usage for a variety of?#CNSdiseases. The advantages of stem cells' ability to accurately mimic the normal?#cellrepair?and development process in the brain drive researchers to explore a new avenue for treating?#neurologicdiseases?[5]. Different types of stem cells, including?#mesenchymalstemcells?(MSCs), fetal neural stem cells, neural cell types differentiated from induced pluripotent stem cells (iPSCs), and?embryonic stem cells?(ESCs), have been transplanted into a model for assessing the therapeutic potential [6, 7].

Adipose-and bone marrow-derived MSCs have a wide application for their capacity to release?#neurotrophicfactors?and the ability to differentiate into a wide variety of cell types [8]. MSCs can create a?#neuroprotective?microenvironment?by releasing specific ILs and cytokines, which is another reason behind its wide use [9]. More those stem cells are immune privileged and not tumorigenic as they are not pluripotent [10].

Recently, Allogeneic MSC engraftments in macaque monkeys have been shown to have varying success due to?#immunogenicity, which can help us frame the future perspective of stem cell transplantation on Huntington's disease. With the overcome of the obstacle of developing long-term cellular therapy, it will be possible to focus on the clinical follow-up with patients to demonstrate the safety and feasibility of this therapy by following the same safety profile they have shown preclinically. It will be possible to develop MSCs to act as a biological delivery system, enabling researchers to test different therapeutic targets for gene delivery using a reliable delivery platform. Astrocytes?and?oligodendrocytes?are widely known to release?trophic factors?that support the growth and repair of partner neurons, it is necessary to study how stem cells can help these two kinds of cells, which will open more possibilities for using stem cells in HDs therapeutic application. SBMF - Associa??o Brasileira de Medicina Farmacêutica #pharmaceuticalmedicine #clinicaltrials #translationalmedicine #translationalresearch

(1)??W.W.?Chen,?X.?Zhang,?W.J.?Huang Role of neuroinflammation in neurodegenerative diseases (Review) Mol Med Rep,?13?(2016), pp.?3391-3396

(2)??A.?Akhtar,?A.?Andleeb,?T.S.?Waris,?M.?Bazzar,?A.R.?Moradi,?N.R.?Awan,?et al. Neurodegenerative diseases and effective drug delivery: a review of challenges and novel therapeutics. J?Contr Release,?330?(2021), pp.?1152-116

(3)??G.M.?Thomsen,?G.?Gowing,?S.?Svendsen,?C.N.?Svendsen. The past, present and future of stem cell clinical trials for ALS. Exp Neurol,?262?(2014), pp.?127-137,

(4)??Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology,?66?(2006), pp.?366-372,

(5)??S.?D,?G.?S,?S.?S,?M.K.?M,?J.M.?H,?I.?D,?et al. Cell therapy: the final frontier for treatment of neurological diseases. CNS Neurosci Ther,?19?(2013), pp.?5-11,

(6)??I.?K,?M.S.?H,?C.W.?V,?S.?G. Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges. Stem Cell Res Ther,?6?(2015)

(7)??B.?C. Concise review: the use of stem cells for understanding and treating huntington's disease. Stem Cells,?36?(2018), pp.?146-160,

(8)??A.?S,?M.?M,?D.?F,?M.?O,?G.?C,?G.?T. Mesenchymal stem cells neuronal differentiation ability: a real perspective for nervous system repair? Curr Stem Cell Res Ther,?6?(2011), pp.?82-92,

(9)??N.K.?V,?S.K.?K,?S.?B,?R.C.?R,?A.?B,?A.?D,?et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease. Transl Res,?155?(2010), pp.?62-70

(10)???????C.?Svendsen. Adult versus embryonic stem cells: which is the way forward?Trends Neurosci,?23?(2000), p.?450.