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Nancy Wexler in Venezuela Huntington’s Disease
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A Huntington's Story
What is Huntington Disease (HD)?
HD affects the entire brain though some areas are worse affected than others.
(Image source: Huntington’s Disease Society of America; www.hdsa.org)
Huntington Disease (HD) is a genetic, progressive brain disorder causing breakdown of nerve cells in the brain. This leads to deteriorating mental and physical abilities of affected individuals ultimately leading to death. Affected individuals present with symptoms like movement issues, cognitive decline, neuropsychiatric issues and emotional disturbances.
Huntington’s disease was first identified in the US in 1872 by George Huntington, the son of a physician who used to ride with his father on medical rounds on Long Island. He once came across two tall, thin women who were twisting and shaking and he concluded they must be suffering from some neurological condition.
HD usually presents itself in the 30s or 40s though it may sometimes come on earlier or later. Juvenile Huntington usually occurs before the age of 20.
There is no cure for HD and treatment is aimed at managing the symptoms and rehabilitation.
HD is caused by a mutation in the Huntington gene (HTT) located on the short arm (p) of chromosome 4 (4p16.3). The HTT gene codes for a protein known as huntingtin which plays an important role in maintaining the health of neurons. The mutated HD gene has abnormally long CAG (cytosine, adenine and guanine) repeats and the length of the repeat may affect the age of onset of symptoms. People with adult-onset HD usually have anywhere between 40 to 50 CAG repeats while those with juvenile HD have more than 60 CAG repeats.
HD is inherited in an autosomal dominant pattern which means one copy of the mutated gene is enough to cause the disease. An affected individual inherits the gene from one of the affected parents. Every child of an affected parent has a 50% chance of inheriting the disease gene.
The HD gene was first identified in 1993 by Nancy Wexler, Higgins Professor of Neuropsychology in the Departments of Neurology and Psychiatry of the College of Physicians and Surgeons at Columbia University. Since 1979, she led a research study in Venezuela which has the largest population of HD and developed a pedigree with more than 18,000 individuals and collected over 4000 blood samples which ultimately led to the identification of the HD gene on the tip of chromosome 4.
- Movement (chorea): rapid, uncontrollable limb movements, unsteady gait, jerky movements and tics
- Forgetfulness: memory loss
- Personality and behavioural changes: aggression, depression, mood swings
- Slurred speech, swallowing difficulties and weight loss: swallowing trouble often leads to malnourishment and extreme weight loss
- Computerized tomography of the brain (CT)
- Magnetic resonance imaging (MRI)
- Electroencephalography (EEG)
- Neurophysiological testing
- Genetic testing to confirm the presence of the mutated HTT gene
Currently, no permanent cure is available for HD though many experimental research studies are in progress. Treatment is aimed at preventing complications and enhancing quality of life as long as possible. An interdisciplinary team of doctors including neurologists, pulmonologists, psychiatrists and physiotherapists will be required to take care of the clinical needs of the individual.
Current treatment includes drugs like tetrabenazine (Xenazine) approved by the FDA in 2008. This drug manages the symptoms of involuntary movements. This is the only specific approved drug for HD. Other symptoms may be managed with drugs like neuroleptic medications. Depression and aggression may require psychotropic drugs.
Individuals with HD require high-calorie food which is easy to chew and swallow.
Supportive treatment may include respiratory support like bipap or ventilators if needed. Physiotherapy is highly recommended to preserve muscle strength. Wheelchairs may be required in some cases. Speech therapy and occupational therapy may be necessary for some individuals.
Investigational therapies like gene therapy and gene editing are in the clinical research stage and proving to be exciting. An exciting new drug on the horizon is RG6042 which went into phase 1 trials and passed the safety test. The drug reduces the buildup of the toxic, mutated huntingtin protein in the brain. The drug has been developed and is being tested by Ionis Pharmaceuticals in Carlsbad, California. In phase 2 trials, around 660 HD patients across the UK, US, Canada and Spain will be involved. 440 will be given the actual drug while 220 will receive a placebo. According to neurologist, John Hardy of University college London; if successful this drug will be the biggest breakthrough for neurodegenerative disorders in the last 50 years.
Living with HD is often traumatic not just for the affected individual but for the families and caregivers. Seeing a loved one lose physical and mental abilities is not easy and often families require emotional support and psychosocial counselling.
People with HD should connect with other affected individuals to gain a sense of solidarity. Patient groups often provide such group support. Caregivers must also explore home assistance to help with the affected individual’s care. It is also advisable to plan for end-of-life care and explore residential homes for the affected individual where he/she will be given robust clinical care.
Look up our list of patient organizations in India for help and support
If there is a known case of HD in the family, it is essential for closest relatives like siblings, uncles, aunts and cousins to test. Many chose not to test to avoid the emotional trauma though.
If a woman with a HD status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.