Rare Disease Report

Chapter 7: Huntington's Disease

Huntington disease (HD) is a genetic, progressive, neurodegenerative disease that typically begins in a person’s 30s, and leads to a rather rapid decline in neuromuscular and cognitive abilities.

Chorea (uncontrolled jerky movements) is the hallmark feature of HD, but other symptoms, like athetosis (relatively slow, writhing involuntary movements), dementia, agitation, and personality disintegration, make this disease a devastating one to have and a difficult one to care for.

HD is an autosomal dominant genetic condition, meaning that if a person has the disease, their offspring has a 50/50 chance of also having it. Since the condition does not manifest itself until a person is well into adulthood, he or she can unwittingly pass it along to their offspring.
 
An interesting phenomenon within the HD community is that many people who know they are at risk for HD do not want to be genetically tested to see if they will acquire it. Most prefer not knowing what the future has in store. This means that the pool of people at risk for HD who are able to participate in studies looking at the natural progression of the disease and/or possible preventive treatments is limited.

The cause of HD is a mutation in the huntingtin gene, located on chromosome 4, which is responsible for the synthesis of the protein huntingtin, of which a specific function is not currently known.
 
For people with, or at risk of, HD who want to have a child: pregenetic diagnostic testing can be used with in vitro fertilization to make sure that any fertilized egg implanted does not have the abnormal gene. This can be done without informing the at-risk patient whether or not they have the mutated Huntingtin gene.

Signs and Symptoms
The severity of the signs and symptoms of HD will vary from person to person, but certain traits are common for most patients. They include:

Neurological changes:
  • Chorea
  • Athetosis
  • Loss of coordination
  • Difficulty swallowing, talking
Emotional changes:
  • Depression
  • Apathy
  • Anxiety
  • Obsessive behavior
  • Irritable
Cognitive changes:
  • Impaired decision-making abilities
  • Poor memory
  • Impaired vision
In the early stages of HD, symptoms that include fidgeting, twitching, excessive restlessness, and/or slight changes in mood may be overlooked. Even if diagnosed, people with early-stage HD (first year or 2) can function quite well both at work and in the home. As the disease progresses, symptoms worsen, chorea becomes more pronounced, and a patient’s cognitive and psychological decline will become increasingly apparent. Many will be unable to work or manage a household, but with assistance, can perform most daily tasks.

Eventually, patients with HD will show less involuntary movements and more rigidity. People in these later stages can no longer manage the activities of daily living and commonly require professional assistance. Death usually occurs 15 to 25 years after the onset of the disease.

Approximately 30,000 individuals in the United States have HD. An additional 200,000 are at risk of developing the condition. There is also a juvenile form, in which the disease severity and progression tend to be more aggressive.  Approximately 10% of the HD community is believed to have the juvenile form.

Treatment
There is not currently a cure for HD, and no known therapy can delay its progression, but there are 2 orphan drugs approved for patients: Xenazine (tetrabenazine) and Austedo (deutetrabenzine) tablets. Both are indicated for the treatment of chorea associated with the condition.

Several treatments are in development for HD. Pridopidine, a dopaminergic stabilizer, is undergoing a phase 3 study, while phase 2 trials are underway for VX15, PED10A inhibitor, cysteamine, and laquinimod.

For more information about these trials, visit hdsa.org/hd-research/therapies-in-pipeline/

Patient Support
There is an array of rare disease and neurological advocacy groups available to assist patients with HD and their families, including the National Organization for Rare Disorders (NORD; rarediseases.org). The prominent advocacy group specifically focused on HD, though, is the Huntington’s Disease Society of America (HDSA; hdsa.org).

The catalyst for HDSA was Marjorie Guthrie, widow of American folk singer Woody Guthrie, who died from the disease in 1967. There are currently 54 HDSA chapters and affiliates across the United States, with the headquarters located in New York City. Grants are available from HDSA for researchers interested in HD. For more information, visit the website.
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