What is Huntington’s Disease?
Huntington’s disease (HD) is a progressive, inherited neurological disorder in which specific nerve cells in the brain gradually deteriorate, producing a characteristic combination of movement, cognitive, and psychiatric disturbances. Early signs often include subtle changes in coordination, involuntary jerking or writhing movements (chorea), and difficulties with balance or fine motor tasks; over time these motor symptoms typically become more pronounced and interfere with everyday activities. Alongside movement problems, HD causes cognitive decline — trouble with memory, planning, and the ability to organize or complete complex tasks — and a range of emotional and behavioral changes such as depression, irritability, apathy, and impulsivity. Because the disease slowly damages brain regions that regulate voluntary movement, thinking, and mood, its course is usually gradual, extending over many years; severity and the exact pattern of symptoms vary considerably between individuals, but HD eventually leads to significant disability and increased care needs. There is currently no cure that halts or reverses the disease, so clinical care focuses on symptom management, supportive therapies, and multidisciplinary care to preserve quality of life for as long as possible.
Professors Ed Wild and Sarah Tabrizi led the UK part of the trial
The history of Huntington’s disease
The condition now called Huntington’s disease was first clearly described in 1872 by Dr. George Huntington, who observed and reported a pattern of hereditary, progressive jerky movements and mental decline in several families in East Hampton, New York. Huntington’s keen clinical observations emphasized both the familial transmission and the progressive nature of the disorder, and his name has been attached to the condition ever since. Over the twentieth century, clinicians and researchers elaborated the clinical spectrum of HD — recognizing juvenile-onset cases, defining stages of progression, and documenting the psychiatric as well as motor features — but the biggest breakthrough came in 1993 with the discovery of the specific genetic mutation responsible: an abnormal expansion of a repeated DNA sequence in the HTT gene. That genetic finding transformed diagnosis, enabled precise predictive testing, clarified inheritance risk, and opened the door to targeted biological research aimed at understanding how the mutant huntingtin protein causes neuronal dysfunction and death. Since then, advances in neuroimaging, molecular biology, and therapeutics research have progressively refined our understanding of disease mechanisms and shaped approaches to patient care and genetic counseling.
Genetic basis and risk factors
Huntington’s disease is caused by a CAG trinucleotide repeat expansion in the HTT gene, which encodes the protein huntingtin. In healthy individuals the CAG repeat is present at a lower number; when the repeat expands beyond a critical threshold, the mutant huntingtin protein gains harmful properties that lead to neuronal injury. A key feature of the genetics is that HD follows an autosomal dominant inheritance pattern: a person who carries the expanded HTT gene has a 50% chance of passing it to each child. The number of CAG repeats also correlates broadly with clinical features — generally, a larger repeat length is associated with earlier onset and, in some cases, faster progression — and the phenomenon of anticipation can lead to longer repeats and earlier onset in successive generations, especially when the mutated allele is inherited from the father. Although the genetic mutation is the primary driver, other genetic modifiers and non-genetic factors — such as overall health, lifestyle, and possibly environmental exposures — can influence the age at onset and the rate of symptom progression. Diagnosis is reliably confirmed through genetic testing, which detects the number of CAG repeats; because testing has profound implications for patients and family members, it is typically offered with genetic counseling to explain the medical, psychological, and reproductive consequences. Current clinical management emphasizes symptomatic treatments (for movement disorders, psychiatric symptoms, and cognitive issues), rehabilitative therapies, and emerging research into disease-modifying strategies — for example, approaches that aim to lower levels of mutant huntingtin or to protect vulnerable neurons — although such therapies remain an active area of study rather than established cures.