Huntington's disease (HD) results from genetically programmed degeneration of brain cells, called neurons, in certain areas of the brain. This degeneration causes uncontrolled movements, loss of intellectual faculties, and emotional disturbance. The disease affects approximately one in 10,000 persons. It is caused by an autosomal dominant mutation, on either of an individual's two copies of a gene called Huntingtin, which means any child of an affected parent has a 50% risk of inheriting the disease.
Most people with Huntington's disease develop signs and symptoms in their 40s or 50s, but the onset of disease may be earlier or later in life. When disease onset begins before age 20, the condition is called juvenile Huntington's disease. Earlier onset often results in a somewhat different presentation of symptoms and faster disease progression.
Symptoms of the disease can vary between individuals and among affected members of the same family, but the symptoms progress predictably for most individuals. The earliest symptoms are a general lack of coordination and an unsteady gait. As the disease advances, uncoordinated, jerky body movements become more apparent, along with a decline in mental abilities and behavioral and psychiatric problems. Physical abilities are gradually impeded until coordinated movement becomes very difficult. Mental abilities generally decline into dementia. Complications such as pneumonia, heart disease, and physical injury from falls reduce life expectancy to around twenty years after symptoms begin. The rate of disease progression and the age of onset vary from person to person.
Medications are available to help manage the symptoms of Huntington's disease, but treatments can't prevent the physical, mental and behavioral decline associated with the condition.
In HD, a defective gene produces an abnormal form of a protein named huntingtin. This abnormal protein triggers a process that kills neurons in a brain region called the corpus striatum and leads to the symptoms of the disorder. The abnormal protein aggregates, or clumps together, inside many kinds of neurons. Some researchers believe these clumps contribute to the problems seen in HD, although it is not yet clear if this is the case. Previous studies have found that cystamine inactivates an enzyme called transglutaminase which helps create the clumps of huntingtin protein.
In the study, lead scientist Marcela Karpuj, Ph.D., and colleagues injected cystamine into mice with an abnormal huntingtin gene. The mice that received the drug had fewer tremors and other abnormal movements and less weight loss than the untreated mice. They also lived about 20 percent longer. However, cystamine did not reduce the number of huntingtin clumps found in the brain.
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