The Abu Dhabi Stem Cell Centre (ADSCC) has achieved a new scientific breakthrough in Huntington’s disease research after its team identified a previously unreported biological mechanism that is believed to play a central role in the progression of the disorder, in a finding that could open the door to future treatments for this rare inherited neurological condition.
Huntington’s disease is a degenerative genetic disorder of the brain that gradually impairs movement, cognitive ability and behaviour. At present, available treatments are limited to easing symptoms rather than addressing the root cause of the disease.
Patient-derived stem cells reveal a new focus
The research team relied on a patient-derived stem cell technique, collecting cells from the skin and blood of patients at different stages of life, including a nine-year-old child, as well as middle-aged patients and others in advanced stages of the disease. These cells were then reprogrammed into induced pluripotent stem cells, enabling the researchers to build laboratory models that mimic brain tissue and include neurons and astrocytes, with the aim of examining the disease mechanisms in high detail.
The study found that astrocytes, which make up the largest proportion of supporting cells in the brain and play a fundamental role in maintaining its functions, are a key element in the development of Huntington’s disease, challenging the long-held scientific view that has for decades focused primarily on neurons as the main driver of the condition.
Mutant huntingtin disrupts critical molecular pathways
The results showed that mutant huntingtin protein disrupts three molecular mechanisms responsible for regulating the production of glial fibrillary acidic protein. This causes astrocytes to lose their natural structure and function and affects the integrity of brain tissue, contributing to the progression of the disease.
To verify the findings, the researchers induced the same defect in healthy cells and then tested three drug compounds that reactivated these mechanisms. This enabled the astrocytes to regain their normal structure and function. Genetically modified animal models of Huntington’s disease, including fruit flies, also showed a marked improvement in movement and climbing after treatment, strengthening the therapeutic potential of this approach and paving the way for further studies.
Broader potential for complex neurological and genetic disorders
The study also highlighted the wide potential of the patient-derived stem cell platform developed by ADSCC in the study of complex genetic and neurological diseases, including amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, Alexander disease, sickle cell anaemia and other genetic disorders causing brain damage and rare diseases prevalent in the region.
The findings are expected to be published soon in a peer-reviewed scientific journal, marking another milestone in the research record of the Abu Dhabi Stem Cell Centre and reinforcing its role in developing innovative solutions for complex genetic and neurological diseases.
Consultant in haematology and bone marrow transplantation, executive director of the Abu Dhabi Bone Marrow Transplant Programme at the Abu Dhabi Stem Cell Centre, and board member of ADSCC and Yas Clinic Group, Dr Fatima Al Kaabi, said: “This scientific achievement represents an important step in the centre’s journey to advance regenerative medicine and cell therapy research, and reflects its commitment to transforming scientific discoveries into future therapeutic solutions.”
Al Kaabi added that: “Investing in scientific research and innovation strengthens Abu Dhabi’s position as a global centre for advanced medical sciences, while the development of research platforms based on patient-derived stem cells provides a deeper understanding of complex genetic diseases and accelerates the development of more precise and effective treatments.”
For his part, Professor Angelo L. Vescovi, professor of cell biology and the study’s principal investigator, said: “The study’s results showed for the first time the pivotal role of astrocytes in the progression of Huntington’s disease after decades of focus on neurons.” He added that restoring their normal function could represent a new therapeutic approach, noting that one of the drug compounds included in the study is already in phase three clinical trials for another disease, which could speed up the assessment of its therapeutic potential for Huntington’s disease in the future.