Abu Dhabi Stem Cells Centre discovers new potential treatment target for Huntington’s disease

UAE— The Abu Dhabi Stem Cells Centre (ADSCC) has reported a scientific breakthrough in Huntington’s disease research after identifying a previously unrecognised mechanism that could provide a new target for developing treatments for the inherited neurological disorder.

The findings, generated using patient-derived stem cells and advanced brain models, could support the development of targeted therapies for Huntington’s disease, which progressively damages movement, cognitive function and behavioural control.

 Despite decades of research, available treatments remain limited and do not address the underlying cause of the disease.

Study identifies role of astrocytes

To investigate the mechanisms driving the disease, ADSCC researchers collected skin and blood cells from patients at different stages of Huntington’s disease, including children and adults.

They reprogrammed the cells into induced pluripotent stem cells (iPSCs) and then differentiated them into brain tissue containing neurons and astrocytes.

This approach enabled the team to study disease processes in a patient-specific laboratory environment.

 The research showed that disease progression may involve not only neurons but also astrocytes, specialised support cells that play a critical role in maintaining healthy brain function.

Specifically, researchers found that mutant huntingtin protein prevents astrocytes from developing and maintaining their internal structural framework.

Further analysis showed that the abnormal protein disrupts three molecular pathways that regulate the production of glial fibrillary acidic protein (GFAP), a structural protein essential for normal astrocyte function.

Potential therapeutic approach

The team subsequently introduced mutant huntingtin protein into healthy cells and reproduced the cellular abnormalities observed in patients.

Researchers then tested three therapeutic compounds that can restore the disrupted molecular pathways.

Following treatment, the affected astrocytes recovered their normal structure and function. The researchers also validated the findings using genetically engineered fruit fly models of Huntington’s disease.

Untreated flies showed impaired movement and reduced climbing ability, whereas treated flies demonstrated significant improvements in motor function.

 These results provided preclinical evidence supporting further investigation of the therapeutic approach.

The researchers said the patient-derived stem cell platform could also advance research into other inherited neurological and genetic disorders, including amyotrophic lateral sclerosis (ALS), leukodystrophies, Alzheimer’s disease, Parkinson’s disease, Alexander disease and sickle cell disease.

Researchers highlight potential for clinical translation

Dr Fatima Al Kaabi, Consultant Haematologist and Bone Marrow Transplanter, Executive Director of the Abu Dhabi Bone Marrow Transplant Programme at ADSCC and Board Member of ADSCC/Yas Clinic Group, said the research reflects the centre’s commitment to advancing scientific discovery and translating research into potential therapies.

Professor Angelo L. Vescovi, Professor of Cell Biology and lead researcher, said Huntington’s disease research had focused primarily on neurons for more than three decades.

However, the study indicates that astrocytes may play a more significant role in disease progression than previously recognised.

He added that identifying the molecular mechanisms underlying astrocyte dysfunction could provide a new biological target for future Huntington’s disease therapies.

 One of the compounds tested is already undergoing Phase III clinical trials for another indication, potentially supporting faster clinical development if subsequent research confirms its safety and effectiveness in Huntington’s disease.

The findings are expected to be published in a peer-reviewed scientific journal.