Cell therapy in Huntington disease

Abstract

<jats:p>✓ Huntington disease (HD), caused by polyglutamate expansions in the huntingtin protein, is a progressive neurodegenerative disease resulting in cognitive and motor impairments and death. Neuronal dysfunction and degeneration contribute to progressive physiological, motor, cognitive, and emotional disturbances characteristic of HD. A major impetus for research into the treatment of HD has centered on cell therapy strategies to protect vulnerable neuronal cell populations or to replace dysfunctional or dying cells. The work underlying 3 approaches to HD cell therapy includes the potential for self-repair through the manipulation of endogenous stem cells and/or neurogenesis, the use of fetal or stem cell transplantation as a cell replacement strategy, and the administration of neurotrophic factors to protect susceptible neuronal populations. These approaches have shown some promising results in animal models of HD. Although striatal transplantation of fetal-derived cells has undergone clinical assessment since the 1990s, many cell therapy strategies have yet to be applied in the clinic environment. A more thorough understanding of the pathophysiologies underlying HD as well as the response of both endogenous and exogenous cells to the degenerating brain will inform their merit as potential therapeutic agents and enhance the framework by which the success of such strategies are determined.</jats:p>

Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation

“…Human neural progenitor cells (hNPCs) are considered as a therapeutic tool for treatment of neurological diseases such as Parkinson's and Huntington's diseases, spinal cord injury and stroke [1][2][3]. hNPCs can be first differentiated, in vitro, into the desired type of neurons, which are sequentially used for transplantation treatment [1].…”

Neurodegeneration and Ageing: A Fatal Encounter

“…Cell therapy aims to replenish the neuronal cells those are degenerated during the course of disease progression [91]. Extensive work has been performed on transplanting foetal-derived cells into the brain of HD patients.…”

“…It has been proposed that these non-neuronal cells may increase the efficacy of stem cell therapy in HD by performing neuroprotective role in degenerative environment, as it is believed that in HD, the key factors driving neurodegeneration are the aberrations in the neurons' surrounding microenvironment rather than the inherent neuronal properties [91]. Subsequently, several reports indicate that astrocytes might interact with NSC to promote their propagation and differentiation thus helping newly formed neuron to integrate in brain neural circuit to make functional mature neuron [102].…”

Tissue Engineering for Tissue and Organ Regeneration

“…An increasing number of studies performed with foetal tissue, ES cells or NSC grafts, mostly in quinolinic acid (QA)-induced animal models of the disease (Clelland et al, 2008) gave successful results leading to clinical trials with foetal-derived cells. However, cell therapy for HD, an incurable disease, is still not widely available in clinic due to ethical, logistical or safety concerns (Kelly et al, 2009).…”