Prion-like mechanisms in neurodegenerative disease: Implications for Huntington's disease therapy

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansions in the huntingtin gene resulting in the synthesis of a misfolded form of the huntingtin protein (mHTT) which is toxic. The current treatments for HD are only palliative. Some of the potential therapies for HD include gene therapy (using antisense oligonucleotides and clustered regularly interspaced short palindromic repeats-Cas9 system) and stem-cell-based therapies. Various types of stem cell transplants, such as mesenchymal stem cells, neural stem cells, and reprogrammed stem cells, have the potential to either replace the lost neurons or support the existing neurons by releasing trophic factors. Most of the transplants are xenografts and allografts; however, recent reports on HD patients who received grafts suggest that the mHTT aggregates are transferred from the host neurons to the grafted cells as well as to the surrounding areas of the graft by a "prion-like" mechanism. This observation seems to be true for autotransplantation paradigms, as well. This article reviews the different types of stem cells that have been transplanted into HD patients and their therapeutic efficacy, focusing on the transfer of mHTT from the host cells to the graft. Autotransplants of reprogramed stem cells in HD patients are a promising therapeutic option. However, this needs further

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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