Huntingtons+Disease

=Huntington Disease= // Sebastian M. Newton // // Ms. Ruebe // // Science, p.7 MYP 10 // // March 8, 2012 // = =

**First Look at Huntington Disease.**

This disorder was first described in 1827 by the American physician George Huntington. His research and hypothesis would not have been possible without the aid of his father and grandfather, who were both renowned physicians. At the age of 22, one year after having been granted the right to practice medicine, George Huntington submitted his first clinical report in which he combines medical knowledge with his own, naming and classifying the disorder. The paper was made with such understanding, lucidness and clinical knowledge that it has not ceased to impress doctors throughout time.

**How it works** Huntington disease or Huntington chorea is a “disorder passed down through families in which nerve cells in the brain waste away, or degenerate.”1 Basically this disease ends up affecting a person´s ability to talk, think and move.

This disorder can present itself in two different variations, the first—and by far most common—is adult-onset Huntington disease in which the afflicted person will start developing symptoms between the ages of thirty and forty. The second and more tragic variation is the early-onset Huntington disease, in which the afflicted person will start developing the symptoms at an early age, this can develop around childhood and adolescence only about 6% of all Huntington disease patients develop the disorder with such an age. Huntington disease is an autosomal-dominant hereditary—If a disease is “Autosomal-dominant” this would mean “you only need to get the abnormal [|gene] from one parent in order for you to inherit the disease”2—disease that is cause by a gene malfunction in chromosome four.“ Normally, the coding region of this gene contains the DNA sequence "CAG" repeated again and again. The number of times this triplet is repeated varies from person to person, ranging from 10 to 26 times.”3 However, people who are afflicted by Huntington disease have an abnormal amount of triplets, ranging from 40 and above. How does the extra amount of protein affect brain cell deterioration is currently unknown, yet it is speculated that somehow the brain cells of the patient start storing high amounts of protein that becomes toxic over time, thus deteriorating his brain cells and producing cell death. “Some patients lose more than 25% of their brain cells before they die.” 4

Detecting Huntington Disease
Since this disease is autosomal and one of the parents has Huntington then there is a 50%/50% chance that the child will end up having the infected set of chromosomes from one parent. If a woman wished to know if her baby is going to have Huntington, then she would be able to go under two different tests while the child is still on her womb. The first is amniocentesis, in which a sample of fluid is extracted from around the fetus, further examination of this fluid can conclude if the baby will or will not have Huntington. The second is chorionic villus sampling—(CVS)—for short, in this test the doctor can remove some fetal cells from the placenta and run some tests on them. Once the child is born, the doctor can conduct physical and emotional evaluations as well as a gene test to determine if the child has in fact Huntington. In juvenile akinetic-rigid Huntington—another name for early-onset Huntington— the family will notice the beginning of the disease because of the symptoms that come with it. The physical symptoms are usually the first to be noticed, as cognitive and psychiatric symptoms are generally not severe enough to be recognized on their own at the earlier stages, a slight stumble when someone walks or random twitches. This physical deterioration is also present in adults and can be taken as the symptoms that would describe the first stage of Huntington. A simple blood test will now determine if you have Huntington or not.

The early symptoms of HD can include:
Apart from the physical symptoms of HD, there are often very subtle intellectual or emotional signs as well, such as: If a person has emotional outbursts, does something clumsy or forgets a task it is not necessarily a sign that they have HD. These things can be just as easily experienced by a person who does not have the defective gene at all.
 * forms of nervous activity like fidgeting, minor twitching in fingers and toes;
 * excessive restlessness;
 * some clumsiness;
 * slight alterations in handwriting; and
 * minor difficulty with normal daily physical skills like driving.
 * short-term memory loss;
 * less ability to organise routine tasks or to cope with new situations;
 * periods of depression, apathy and irritability; and
 * impulsiveness.

Advanced Symptoms
As HD progresses the early physical, intellectual and emotional symptoms become more marked. In many cases the person with HD will develop involuntary movements like jerks and twitches of the head, neck, arms and legs. Sometimes, people with HD will develop rigid muscles instead of involuntary movement. All of these physical symptoms can make walking, speech, swallowing and other basic tasks more difficult as the disease progresses.

Cycle.
Usually the disease presents itself in five stages. Patients usually die 15-20 years after they have been diagnosed with the early stage of the disease.
 * Early Stage - the person is diagnosed as having HD and can function fully both at home and work.
 * Early Intermediate Stage - the person remains employable but at a lower capacity. They are still able to manage their daily affairs despite some difficulties.
 * Late Intermediate Stage - the person can no longer work and/or manage household responsibilities. They need considerable help or supervision to handle daily financial affairs.Other daily activities may be slightly difficult but usually only require minor help.
 * Early Advanced Stage - the person is no longer independent in daily activities but is still able to live at home supported by their family or professional care’s.
 * Advanced Stage - the person with HD requires complete support in daily activities and professional nursing care is usually needed.

The treatment
There is no known treatment for Huntington disease; however doctors decide to distribute different pills that can control the emotional state of the afflicted and some that can control a quantity of the spastic movements. Doctors also treat their patients assigning them a series of therapy’s both mental and physical, naturally this helps Huntington patients live more controlled lives. Effects Social: The search for the cause of this condition was enhanced considerably in 1968 when the Hereditary Disease Foundation (HDF) was created by Milton Wexler, a psychoanalyst based in Los Angeles, California whose wife Leonore Sabin had been diagnosed earlier that year with Huntingdon's disease. The three brothers of Wexler's wife also suffered from this disease. The foundation was involved in the recruitment of over 100 scientists in the Huntington's Disease Collaborative Research Project who over a 10 year period worked to locate the responsible gene. Thanks to the HDF, the ongoing US-Venezuela Huntington's Disease Collaborative Research Project was started in 1979, and reported a major breakthrough in 1983 with the discovery of the approximate location of a causal gene. This was the result of an extensive study focusing on the populations of two isolated Venezuelan villages, Barranquitas and Lagunetas, where there was an unusually high prevalence of the disease. It involved over 18,000 people - mostly from a single extended family.

A disease such as this one is also known to break the hearts of familiars and friends as they see a person they knew, loved, respected and cared for being slowly degraded to a hollow memory of who he was before. Economical: While on the search of the gene that caused Huntington, the project developed DNA-marking methods which were an important step in making the Human Genome Project possible. In 1993, the research group isolated the precise causal gene at 4p16.3, making this the first autosomal disease locus found using genetic linkage analysis. Thanks to the research of this disease it was how the idea of DNA-marketing hit the companys, suddenly everyone was participating in the Human Genome project and patenting parts of the human genome creating an economical charge. So in looking for the specific gene that caused Huntington, the scientist indirectly introduced a way to make money out of the discovery of other genes.

To be such a dire disease, Huntington has actually had some positive impacts on science and medicine. For instance, this disease being so common and tragic has aroused the curiosity of many scientists, within this mass, many ideas have been produced and experimented with; in order to cure this disease. Gene silencing is “the Interruption or suppression of the expression of a gene at transcriptional or translational levels.” 5 This means that scientists are able to shut off some genes. This idea has been tested and tried many times during a thirty year period, yet all attempts have failed. However with time come new people and with this people new ideas. Dr. Jan Nolta, is currently leading a team of scientist using a type of bone marrow to get a gene silencing drug into the brain. Theorically if this was to work on people, then Huntington patients would be relieved of the symptoms of their illness. However it does not end there, gene silencing could be used to carry other drugs, not only HD silencing drugs. Thus bringing a new cure to neurological diseases all across the board, it is this idea that has led to many people trusting their hope on this solution. Another thing that functions as a positive impact is the ability that Huntington disease patiens have to become sick, “ studying otherwise healthy-appearing individuals who have nearly 99% certainty of manifesting the symptoms of brain disease does provide distinct but valuable information about the true natural history of the disease. The field has witnessed an explosion of research examining possible early indicators of Huntington’s disease during what is now referred to as the ‘prodrome’ of Huntington’s disease. A NIH study in its 9th year (PREDICT-HD) has offered a glimpse into the transition from an apparently healthy state to an obviously diseased state, and can serve as a model for many other genetic diseases, both neurological and non-neurological.” 6 An interesting thing about Huntington disease is the effect that it has on people when they are healthy, it seems the overload of protein p53, causes the patients to become healthier making them live early years with an extremely healthy condition.

The limitations
Sadly all is not prosperity and felicity with this disease, there are also many negatives aspects to it. For example, the way the extra released protein into the brain creates the sickness is still unknown, so scientist don’t actually know how this disease is caused, how can one treat something he barely knows? Other negative things about the disease would be the terminality of it all. Currently if you’re diagnosed with Huntington then you face the fact that you will die, but faster, and worst you will die not truly being you, because this disease is known to also warp a person’s personality. With so many failed attempts for curing this takes a toll on the moral of scientists work knowing that the probability of failure is much greater than that of success.

Conclusion.
There are many benefits on cracking Huntington disease, yet there are also many limitations on the ways to crack it. Many have lost hope on finding a cure for such a heartbreaking disease, but there are those who still trust in science and in the people operating it.

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Works Cited “Autosomal Dominant.” //MEDLINE//. U.S. Nationall Library of Medicine, n.d. Web. 10 Mar. 2012. . Carroll, Jeff, and Ed Wild. “Could mesenchymal stem cells deliver gene silencing drugs?” //HD BUZZ// 31 Jan. 2012: n. pag. //HD BUZZ//. Web. 10 Mar. 2012. <http://en.hdbuzz.net/‌70>.

Enquiries. “Huntington Disease.” //Huntington Disease Whales//. N.p., n.d. Web. 10 Mar. 2012. <http://www.ahdansw.asn.au/‌information/‌faq_symptoms.html>.

“Gene Silencing.” //NCBI//. Probe, n.d. Web. 8 Mar. 2012. <http://www.ncbi.nlm.nih.gov/‌projects/‌genome/‌probe/‌doc/‌ApplSilencing.shtml>.

Paulsen, Jane S. “Future Neurology.” //Future Technology//. N.p., n.d. Web. 10 Mar. 2012. <http://www.futuremedicine.com/‌doi/‌abs/‌10.2217/‌fnl.09.78>.

Walker, Francis O. “Huntington Disease.” //The Lancet//. N.p., n.d. Web. 11 Mar. 2012. <http://www.thelancet.com/‌journals/‌lancet/‌article/‌PIIS0140-6736(07)60111-1/‌fulltext>.

Tufts University. "Biologists Link Huntington's Disease To Health Benefits In Young." ScienceDaily, 25 Sep. 2007. Web. 13 Mar. 2012. Genetic Science Learning Center. "Huntington's Disease." Learn.Genetics 12 March 2012 <http://learn.genetics.utah.edu/content/disorders/whataregd/hunt/>