Stem Cells Highlighted as Potential Therapeutic Option in Huntington Disease

Although no pharmacological treatment offers long-term efficacy or extends survival with Huntington disease at this point, research suggests that stem-cell therapy holds promise in this and other neurodegenerative diseases.

The current treatment paradigm for patients with Huntington disease (HD) addresses symptom relief rather than slowing disease progression, but a review of early research presents stem cell transplantation as a potentially curative tool for the rare and fatal condition.

HD is a rare, inherited neurodegenerative disorder characterized by progressively worsening movement and affective abnormalities, dementia, and cognitive impairment. It is caused by repetitive cytosine, adenine, and guanine (CAG) or glutamine expression on the coding region of the huntingtin gene (HTT), and symptoms typically manifest in older adults. While no pharmacological treatment offers long-term efficacy or extends survival at this point, research suggests that stem-cell therapy holds promise in HD and other neurodegenerative diseases.

There are several types of stem cells, with main types including embryonic stem cells (ESCs), adult stem cells (ASCs), and a combination of the 2 called induced pluripotent stem cells (iPSCs). Stem cells in general have the ability to differentiate into various types of cells. ASC subtypes include mesenchymal stem cells (MSCs) and neural stem cells (NSCs), each of which has unique applications. All of these stem cells have been researched in the context of neurodegenerative disease, and several stem-cell therapies have been approved for central nervous system diseases.

The current treatment strategy for HD includes symptom reduction, as no therapies are able to address the underlying mechanisms of the disease. Speech, physical, and occupational therapy are often incorporated in addition to pharmacologic agents.

“From various clinical studies and research, it has been established that cell therapies can potentially restore tissue atrophy,” the study authors wrote. “Hence, stem cell therapy can be a flourishing therapeutic strategy as a targeted approach to replace the dysfunctional cells in HD.” The review highlights MSCs, iPSCs, ESCs, and NSCs as potential therapeutic routes in HD.

MSCs have been studied in rodent models of HD and were found to improve motor function and anxious behavior, in addition to potentially improving lifespan by mitigating the clinical progression of the disease. Also in rodent models, iPSCs were shown to improve behavior and motor abilities. ESCs were found to differentiate into neurons, oligodendrocytes, and astrocytes—which may enhance neuronal function and brain development—when introduced to transgenic mouse models. However, adverse effects such as the rejection of immune response and tumor progression when using ESCs. Finally, NSCs have shown potential in both primate and mouse models of HD, improving motor function and overall function. With both ESCs and NSCs, ethical concerns may arise that must be considered.

The results of different stem-cell–based neural repair strategies have varied between models, making it difficult to draw conclusions on which have the most potential in HD treatment. “But as it is possible through stem cell reprogramming technology to generate patient-derived cellular models of HD, [which] can help us in multiple ways such as understanding the pathogenesis of the disease and finding out potential therapeutic approaches,” the authors wrote.


Saha S, Dey MJ, Promon SK, Araf Y. Pathogenesis and potential therapeutic application of stem cells transplantation in Huntington's disease. Regen Ther. Published online September 25, 2022. doi:10.1016/j.reth.2022.09.001

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