Biology 202
1998 Fi

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Huntington's Disease - An Overview

Christy Taylor

Huntington's Disease is a devastating and progressive neurological disorder that resu lts primarily from degeneration of nerve cells deep in the center of the brain. The condition was first described by George Huntington, a physician in New York, in 1872. Even then, the physician recognized the all-encompassing factors of the disorder when describing it as, "coming on gradually but surely, increasing by degrees, and often occupying years in its development until the hapless sufferer is but a quivering wreck of his former self".

The three most profound behavioral problems in Huntington 's disease come from the uncontrollable movements called "chorea," dementia, and the altered perception of the world. The course of Huntington's Disease can last anywhere from ten to 30 years from onset to death. The symptoms of HD usually develop when th e person is between the ages of 30 - 50 years, although they have been known to occur as young as two and as old as 70. It affects all races and ethnic groups and occurs with the same frequency in both men and women.

As the disease progresses, the se verity of the symptoms increase and can be divided into three stages. The first stage is characterized by subtle and slight uncontrollable muscular movements, including stumbling and clumsiness, lack of concentration and short-term memory lapses, and depr ession and changes of mood. In the middle of the disease's course, patients may need assistance with some daily activities because walking, speech and swallowing abilities deteriorate. Involuntary movements become more pronounced and may be noticeable to the casual observer. In the latter stages, patients with HD require full-time care, and often families opt to place their loved ones in nursing homes. Patients may no longer be able to speak or talk; rigidity may now be more of a problem than involuntary movements; feeding tubes often have to be used because patients can no longer swallow. However, even as the disease progresses, people with the disorder almost always recognize their families, are aware of the situation, and have the ability to understand . Death usually occurs by aspiration pneumonia, malnutrition, or heart failure.

At present, there is no cure for the disease, but dynamic progress has been made as researchers explore this illness. HD is inherited as an autosomal dominant condition. In March 1993, scientists realized that HD is caused by a mutation in a gene located on chromosome 4. This gene has a unique genetic sequence for CAG (cytosine-adenine-guanine) and codes for the amino acid glutamine, a building block for the huntingtin pr otein. Normal individuals have this sequence duplicated from 11 to 40 times in their genetic coding without having symptoms of HD. However, individuals with the disease have from 40 up to 100 repeated CAG segments. Juvenile Huntington's Disease occurs wit h 60 or more repeats, linking the longer chains of CAG sequences to earlier and more aggressive onset of the disease.

Current research revolves around the transgenic mouse model developed in Berlin at the Max Planck Institute. The model was made by p utting the first part of the HD gene, containing the long stutters of CAG repeats, into a mouse, and it was discovered that two months later the mice began to exhibit the changes in behavior and chorea seen in humans. Upon comparing the brains of normal m ice to those that were genetically engineered, Steve Davies recognized that the glutamine-rich regions cause the proteins to clump together over time until they reach a critical mass that triggers their migration into the nucleus of brain cells. This migr ation causes brain cells to become more vulnerable to chemicals in the body leading to cell death. The area of the brain in which the cell death is seen is the basal ganglia. This is a group of nuclei clustered around the thalamus that is responsible for coordinating voluntary movement and for planning and sequencing muscle activity. The complications surrounding the behavioral symptoms seen in HD centers around the fact that "motor systems comprise more than a collection of reflexes and central pattern g enerators (CPG). They also include many neural circuits and centers whose function is to select the behavior to be expressed, control the vigor with which it will be expressed, and decide how long it will last." Most behavior involves more than one type o f neuron for its control and regulation and can be elicited through more than one pathway. Basal ganglia generally exert an inhibitory influence on the thalamus and when this is disrupted movements become exaggerated and uncoordinated.

The mechanism for cell death in the brain is unknown, but researchers currently believe that it is due to over-stimulation of weakened cells by excitatory chemicals that play a normal role in the transmission of nerve impulses. When these excitatory amino acids cause c ell damage, they are known as excitotoxins. Studies have indicated that when quinolinic acid is injected into the basal ganglion region of the brain, the rats exhibit the symptoms of HD because the acid has damaged neurons by overstimulating them. Althoug h the human body naturally produces small amounts of quinolinic acid, it may be particularly damaging in HD patients due to weak, vulnerable cells. Although there is currently no cure for the disease, the research field for treatment and prevention for H untington's is dynamic. Those affected by the disease have seen potential surgical treatments arise within the past few months. These include transplantation of human or pig fetal cells and permanent destructive lesions of the brain (pallidotomy). However , both of these techniques have given inconclusive results. Other research involves drug therapy that would strengthen brain cells and make them less vulnerable to excitatory chemicals or medicine that would block excitatory chemicals altogether. But perh aps the most technological research revolves around a restorative treatment using the drug CNTF. In studies, a capsule containing fibroblasts modified to produce CNTF is placed into the brains of rats which are then injected with an excitatory chemical kn own to cause brain degeneration in rats producing symptoms seen in HD. Research has shown that the medication secreted from the capsule protects the brain cells from degeneration. This research is about to be performed on humans where the pump would be im planted underneath the skin and filled with CNTF that would enter the brain.

There are now 25,000 to 30,000 people afflicted with this disease in the United States. An additional 150,000 are at risk. Although very few cases of HD are due to fresh mu tation, everyone who has the HD gene will eventually develop the disorder unless he or she dies from some other cause before the signs appear. Furthermore, there is often little or no choice of residential care for those with HD, especially in the later s tages of the illness. However, the hope for a cure continues to mount every year and families and communities are joining together to promote better treatment and understanding for those with the disease. Hopefully, a cure will be found in my lifetime.

National Institute of Neurological Disorders and Stroke, "Huntington's Disease: 1992 Research Highlights"

John Lester, "Huntington's Disease"

"About Huntington's Disease," Internet, available:

Debra Collins, "Genetics of Huntington's Disease"

Kathleen Shannon, M.D., "Review of Publications in the Last Year Relating to Huntington's Disease"

Steve Davies, "Scientists Report New Understanding of Cell Death in HD"

Fred Delcomyn,

, (New York: W.H. Freeman and Company, 1998) 437.

James W. Kalat,

, (California: Wadsworth Publishing Company, 1992) 339-340.

"Huntington Study Group Position Statement on Experimental Surgical Treatments in HD"

"Chapter 5 - The Course of the Illness"

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