Researchers have gained a greater understanding of the role inflammation plays in Huntington’s disease progression, to help identify potential therapeutic targets for treatment.

The study was led by University of Galway and investigated whether the degree of inflammation in the midcingulate cortex - a part of the brain that plays a role in emotion processing, decision-making and cognitive control - correlates with the degree of cell death and type and severity of symptoms, particularly mood-related symptoms in Huntington’s disease.

Huntington’s disease is an inherited disease that causes the progressive death of nerve cells in the brain. It has a broad impact on a person's functional abilities and usually results in movement, cognitive and psychiatric problems. Behavioural and psychiatric symptoms are often named the most burdensome for patients and their families, changing family roles, dynamics and relationships.

The study was published in the journal Communications Medicine and can be read here.  

Professor Andrea Kwakowsky, Associate Professor of Pharmacology, School of Pharmacy and Medical Sciences, University of Galway, and lead author, said: “With our society facing an ageing population, Huntington’s disease could become more common, with some patients showing low-grade, late-onset forms of the disease.

“Overall, the results present a complex picture of potential inflammation priming - where cells or tissues exposed to an initial inflammatory signal become more persistent - in the Huntington’s disease midcingulate cortex, rather than a highly active inflammatory response within the central nervous system.

“This research shows that neuroinflammation-related genes are activated in all Huntington’s disease cases, and are particularly strong in cases with dominant motor symptoms compared to those with mood or mixed symptoms.

“The results point to a unique involvement of the midcingulate cortex in motor-specific neuroinflammatory pathology, suggesting it may serve as an early marker of disease progression and merits further study.”

The researchers performed critical experiments to determine the degree of inflammation in the midcingulate cortex and its link to Huntington’s disease symptoms, particularly the behavioural and psychiatric symptoms. They also identified novel genes which are involved in neuroinflammatory processes.

Prolonged inflammation in the brain can be destructive. The physiological symptoms of Huntington’s disease have been linked to neuroinflammation due to the presence of inflammatory mediators - chemical substances released by immune cells, and reactive glial cells - the brain’s fundamental response to damage. Many cell communication pathways likely interact to propagate neuroinflammation in the brain.

Professor Kwakowsky said: “Neuroinflammation is thought to cause cell loss, and cell loss in the cingulate cortex – a brain region that links emotion, cognition, memory and motor function – linked to Huntington’s disease mood symptoms. However, the presence of neuroinflammation in Huntington’s disease of the midcingulate cortex, which manages emotion regulation, has not yet been investigated.”

The study was funded by the University of Galway, Aotearoa Foundation, Centre for Brain Research, the University of Auckland, the Health Research Council of New Zealand, Alzheimer’s New Zealand, Freemasons New Zealand, Neurological Foundation of New Zealand, Maurice and Phyllis Paykel Trust, and the Whau Foundation. 

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