Huntington's: The Anticipation that Kills

After doing research on the effects of the disorder Huntington’s disease, it is easy to understand what a disease like Huntington’s will do to an individual way of life. Imagine being thirty years old with a good job, a loving spouse, maybe a couple of kids and an all-around pretty good life. Then imagine one day your boss writes you up and sends you home because he/she suspects you of being intoxicated. A person in this situation could, in months and years to come, learn from a simple blood test that he/she is the victim of a genetic disorder called Huntington’s disease. The ramifications of this illness are endless and affect not only the individual with the disorder but entire families and communities as well. At this time there is no cure or even any significantly effective treatment. However, as with many genetic disorders, research is being done in in this day in age that may promise to one day lead us to such treatment or cure.
Huntington’s disease is a neurodegenerative or genetic disorder that affects muscle coordination and some cognitive functions, typically becoming noticeable in middle age. It is much more common in people of Western Europe descent than in those from Asia or Africa. The disease is caused by dominant mutation on either of the two copies of a specific gene, located on chromosome 4. The Huntington gene normally provides the genetic code for a protein that is also called Huntingtin. The mutation of the Huntingtin gene codes for a different form of the protein, whose presence results in gradual damage to specific areas of the brain.
The condition Huntington’s disease got its name because it was first described by George Huntington, a physician in New York, in 1872. Examining the combined medical history of several generations of a family exhibiting similar symptoms, he realized their conditions must be linked; he presented his detailed and accurate definition of the disease as his first paper. Sir William Osler was interested in the disorder and was impressed with Huntington’s paper stating that “In the history of medicine, there are few instances in which a disease has been more accurately, more graphically or more briefly described.” It use to be commonly known as Huntington’s chorea – chorea being the Greek word for dancing and describing the strange movements of the sufferer. The illness probably occurs all over the world, though it has not been thoroughly researched in many places, particularly in underdeveloped countries. The illness begins to gradually change the individual behavior such as depression, moodiness, or by unusual jerky, fidgety movements and perhaps unsteadiness of the hands or feet causing falls and a tendency to be clumsy. These are early signs. They are mild and increase so slowly that they may go unnoticed and it is only much later.

These changes are thought to come about because of a disturbance of one of the chemical substances concerned in normal functioning of the brain though it is not known exactly which chemical is involved. Over the years the illness goes on getting more severe, though the rate at which the sufferer has no control, increase, causing falls and making walking difficult. Speech usually becomes slurred and swallowing difficult. Sleep disturbances are also associated symptoms. Juvenile HD differs from these symptoms in that it generally progresses faster and chorea is exhibited briefly, if at all, with rigidity being the dominant symptom. Seizures are also a common symptom of this form of HD. Some individuals will at times become confused and forgetful, at other times angry and unreasonable and possibly violent. Alternatively, some people become quite passive, but the illness has its ups and downs and some days the ungainly movements and irritability are less. This changing state is confusing and frustrating for both sufferers and their families. At present there is no cure, though medicine may lessen the jerky movements, and sympathetic and understanding care can help to keep the sufferer less agitated and so less liable to unreasonable behavior ultimately, it may become too difficult to care for the sufferer at home.
The illness usually lasts fifteen to twenty years, although it may be considerably longer. Death is often from pneumonia because sufferers cannot cough well enough to clear the chest if they have infections. The most common age of onset of the illness is between the age of thirty and fifty years, although it can manifest itself at almost any age. Both men and women are affected and it is estimated that perhaps six – thousand people now have the illness in the United Kingdom. Huntington’s disease hereditary and runs in families in a way that is well understood. It is called a dominant disorder.
It is known for certain that Huntington’s disease is a dominant disorder and that the abnormal gene need to be present on only one member of a gene pair for the individual to develop the disorder. This means that each time an individual who has the gene for Huntington’s disease has a child; there is a one to two chance that the child will inherit the disease. There is also a one to two chance that the child will inherit the normal gene. Everyone who inherits the gene will eventually develop the disorder unless he or she dies from some other cause before the signs appear.
Because they are like their affected parent for example in stature or skin or eye color, some people fear they may also have inherited the gene too. Physical or temperamental likeness to an affected parent does not imply that the child has also inherited gene; nor does it change the one or two risk. It can only be said that, on average, half the children of a sufferer will inherit the gene. This does not mean that precisely two out of four or three out of six children in a family will inherit it, but that every child has a 50/50 chance of getting it. Some families are lucky and perhaps all of their children will escape, other families are probably less fortunate; but the chance for any other child remains one in two.
For some time researchers have known that the gene for the Huntington’s disease was near the end of chromosome four. Since the discovery of the gene in March 1933, a new predicting test has been developed. This can identify the carriers of the faulty gene before they develop the illness. After a number of counseling sessions at a genetic clinic, blood samples are taken form the person who wishes to be tested. The DNA which is extracted from the blood is then analyzed in a special laboratory. Occasionally the result falls in a gray area where it is still uncertain whether the person will develop the disease or not. Even when the test does show that someone has the faulty gene, it still does not show the age at which the disease will start to develop.
Medical diagnosis of the onset of HD can be made following the appearance of physical symptoms specific to the disease. A physical examination, sometimes combined with a psychological examination, can determine whether the onset of the disease has begun. Medical imaging, such as computerized tomography or CT for short, and magnetic resonance imaging or MRI for short, only shows visible cerebral atrophy in the advanced stages of the disease. Functional neuroimaging techniques such as fMRI and PET can show changes in brain activity before the onset of physical symptoms. A positive result is not considered a diagnosis, since it may be obtained decades before the symptoms begin. However, a negative test means that the individual does not carry the expanded copy of the gene and will not develop HD.
There are different types of test which can be carried out on a fetus. This test analyses DNA from several family members using markers linked to the gene. It shows whether the baby is at low risk of inheriting the faulty gene or at the same risk as the parent who is at risk but so far unaffected.
There are different tests for Huntington’s disease. The first, presymptomatic testing is for people who are at risk for the disease. The second, prenatal testing is a testing of a fetus at risk for the disease. The third type of testing, confirmatory testing is used on someone suspected of having Huntington’s disease.
Although the outlook for people today with Huntington’s disease may look grim, significantly research into treatments is underway. Some modes of therapy available today are Botox injections used to calm involuntary twitching in face muscles as well as occupational and physical therapy to offset motor function problems and speech therapy for those who find it hard to communicate. As far as pending research is concerned, the Huntington’s disease Society of America is one of the leading groups who are pioneering new ways to look at the genomic and molecular levels of the disease.

Some areas of their research include examination of the energy needed in the cell mitochondria of the Huntington’s disease patients. They are also researching on the folding of Huntington protein and how it makes the cell unable to dispose of the mutated strain. One more important part they are researching is how the Huntington gene works in normal people versus the affected with the mutated Huntington protein.
A fairly recent and exciting discovery of doctors associated with HDSA suggests a correlation between degenerative diseases like Huntington and cancer. Although they might seem very different at first glance because cancer is characterized by cells that divide to rapidly while Huntington’s disease causes neurons to die, new research shows that the same signal that causes these cancer cells to divide may make brain cells degrade. Yet another possible similarity between cancer and HD involves p53, a tumor mutated and allows cells to divide uncontrollably. Some scientist believe that the mutated Huntington protein could actually over activate p53 and cause brain cells in affected people to slowly die. Also Dr. Robert Friedlander found that a certain enzyme created in the body called caspase -1 which kills off mutated cells in a normal human being may be over activated in HD patients causing the enzyme to kill healthy brain cells. Dr. Friedlander found that he could diminish the function of caspase – 1 with an antibiotic called Minocycline, and in turn he could delay the onset and the progression of the effects of HD in mice.
Huntington’s disease, particularly the application of the genetic test for the disease, has raised several ethical issues. The issues for genetic testing include defining how mature an individual should be before being considered eligible for testing. Ensuring the confidentiality of results, and whether companies should be allowed to use test results for decisions on employment, life insurance or other financial matters. There was controversy when Charles Davenport proposed in 1910 that compulsory sterilization and immigration control be used for people with certain diseases, including Huntington’s disease, as part of the eugenics movement.
The development of an accurate diagnostic test for Huntington’s disease has caused social, legal, and ethical concerns over access to and use of a person’s results. Many guidelines and testing procedures have strict procedures for disclosure and confidentiality to allow individuals to decide when and how to receive their results and also to whom the results are made available. As with other untreatable genetic conditions with a later onset, it is ethically questionable to perform pre – symptomatic testing on a child or adolescent as there would be no medical benefit for that individual. There is consensus for only testing individuals who are considered cognitively mature, although there is a counter – argument that parents have a right to make the decision on their child’s behalf. For example, prenatal testing raises the issue of selective abortion, a choice considered unacceptable by some.

In 1968, after experiencing HD in his wife’s family, Dr. Milton Wexler was inspired to start the Hereditary Disease Foundation, with the aim of genetic illnesses by coordinating and supporting research. The foundation and Dr. Wexler’s daughter, Nancy Wexler, were key parts of the research team in Venezuela which discovered the HD gene. Since then, support and research organizations have formed in many countries around the world and have helped to increase public awareness of HD. A number of these collaborate in umbrella organizations, like the International Huntington Association and the European HD Network.
As one can see, Huntington’s disease is a truly debilitating and emotionally straining disease. It affects people across the globe in every portion of their daily life. Not unlike many diseases today such as Parkinson’s, affected people become 100% dependent on loved ones or medical professionals for activities of daily living once they have progressed to the final stages of HD.One day, sooner or later, the cause will be better understood and a treatment found. This may come in the lifetime of young people who still have to face an uncertain future. We all long for the day when the scourge of this illness, like many others, will be removed from us. In the meantime, families are joining together worldwide to promote better treatment and understanding of those who suffer and to make their needs known.
The International Huntington’s Association crosses all boundaries of race and language and links people in a common cause, to face with courage what cannot be changed and to change what it is in our power to change, working together towards greater knowledge and better services, and above all creating the sense of fellowship that overcomes fear and isolation.