Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the Huntingtin gene (HTT). Current treatments focus on symptom relief and comprehensive care. Innovative gene and cell therapy strategies, such as the use of human iPSC-derived striatal neurons (hStrOs) and human umbilical cord mesenchymal stem cells (hUC-MSCs), are being actively researched. These combination therapies aim to target different cellular, epigenetic, and genetic factors, potentially enhancing therapeutic outcomes. Preclinical studies have shown promising results, and the next step is to design clinical trials to assess the safety and efficacy of these innovative strategies.
Key Insights from the review include:

1. Combination Therapy Potential: The combination of hStrOs and hUC-MSCs leverages the immunomodulatory and neurotrophic properties of hUC-MSCs, enhancing the survival and targeted differentiation of transplanted cells. This approach provides a supportive microenvironment for the grafted cells, promoting effective integration with the host brain’s neural network.
2. Preclinical Success: Promising preclinical results indicate the potential of epigenetic, genetic, and stem cell-based approaches for modifying the course of HD. These strategies have shown significant promise and are strong candidates for future clinical trials.
3. Multifaceted Treatment: Addressing the multifaceted nature of HD requires a combination therapy that targets different cellular, epigenetic, and genetic factors. Such a synergistic approach may offer benefits beyond those of single therapies, potentially leading to more effective management of HD symptoms.

This review highlights the progress in gene and cell therapy for Huntington’s disease, emphasizing the potential of combination therapies to address the complex nature of the disorder. Future research and clinical trials are essential to validate the safety and efficacy of these innovative strategies, which could significantly improve treatment outcomes and ultimately lead to a cure for HD. The work entitled “ Advances in gene and cellular therapeutic approaches for Huntington’s disease” was published on Protein & Cell (published on Aug. 9, 2024).
DOI: 10.1093/procel/pwae042