HUNTINGTON’S CHOREA Dandre Maxey

Woodrow Wilson Guthrie (/ˈɡʌθri/; July 14, 1912 – October 3, 1967) was an American singer-songwriter who is regarded as one of the most significant figures in American folk music; his songs, including social justice songs, such as "This Land Is Your Land", have inspired several generations both politically and musically.[1][2][3] He wrote hundreds of political, folk, and children's songs, along with ballads and improvised works When Woody was 14, his mother was hospitalized due to a strange neurological disorder.By the 1940’s, Woody’s health was declining and his behavior was extremely erratic.In 1952, It was determined he was suffering from Huntington's disease, a genetic disorder inherited from his mother.Increasingly unable to control his muscles, Woody was hospitalized in 1956. During the final few years of his life Guthrie was largely alone except for family. The progression of Huntington's threw Guthrie into extreme emotional states causing him to lash out at those nearby. These actions mirrored common symptoms of Huntington's including uncharacteristic aggression, emotional volatility, and social disinhibition.Guthrie's illness was essentially untreated, because of a lack of information about the disease. His death helped raise awareness of the disease and led his wife, Marjorie to help found the Committee to Combat Huntington's Disease, which later became the Huntington's Disease Society of America

WHAT IS IT

wHAT IS HD Huntington’s disease (HD) is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. It deteriorates a person’s physical and mental abilities during their prime working years and has no cure. HD is known as the quintessential family disease because every child of a parent with HD has a 50/50 chance of carrying the faulty gene. Today, there are approximately 30,000 symptomatic Americans and more than 200,000 at-risk of inheriting the disease

SYMPTOMS INCLUDE Personality changes, mood swings and depression Forgetfulness and impaired judgement Unsteady gait and involuntary movements(chorea) Slurred speech, difficulty in swallowing and significant weight loss

CHOREA Chorea (or choreia, occasionally) is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesia. The term chorea is derived from the Greek word χορεία (=dance; see choreia), as the quick movements of the feet or hands are comparable to dancing

Basal ganglia, group of nuclei (clusters of neurons) in the brain that are located deep beneath the cerebral cortex (the highly convoluted outer layer of the brain). The basal ganglia specialize in processing information on movement and in fine-tuning the activity of brain circuits that determine the best possible response in a given situation

DORSAL STRIATUM Caudate nucleus- plays important role in procedural learning,associative learning and inhibitory control of action Putamen- primary function is to regulate movements and influence various types of learning.It employs GABA, Acetylcholine, and Enkephalin to perform its functions.

Who Is At Risk HD affects both sexes and all races and ethnic groups around the world. Symptoms usually appear between the ages of 30 to 50, and worsen over a 10 to 25 year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure or other complications. Everyone has the gene that causes HD, but only those that inherit the expansion of the gene will develop HD and perhaps pass it on to each of their children. Every person who inherits the expanded HD gene will eventually develop the disease. Over time, HD affects the individual’s ability to reason, walk and speak. In approximately 10% of cases, HD affects children or adolescents. The symptoms for JHD(Juvenile HD) may include stiff or awkward walking ,increased clumsiness or changes in speech. Every child of a parent with HD has a 50/50 chance of inheriting the expanded gene that causes the disease. If the child has not inherited this expanded gene , he or she will never develop the disease and cannot pass it to their children.

HD is one of several trinucleotide repeat disorders which are caused by the length of a repeated section of a gene exceeding a normal range.[25] The HTT gene is located on the short arm of chromosome 4[25] at 4p16.3. HTT contains a sequence of three DNA bases—cytosine-adenine-guanine (CAG)—repeated multiple times (i.e. ... CAGCAGCAG ...), known as a trinucleotide repeat.[25] CAG is the 3-letter genetic code (codon) for the amino acid glutamine, so a series of them results in the production of a chain of glutamine known as a polyglutamine tract (or polyQ tract), and the repeated part of the gene, the PolyQ region.[26] All humans have two copies of the Huntingtin gene (HTT), which codes for the protein Huntingtin (HTT). The gene is also called HD and IT15, which stands for 'interesting transcript 15'. Part of this gene is a repeated section called a trinucleotide repeat, which varies in length between individuals and may change length between generations. If the repeat is present in a healthy gene, a dynamic mutation may increase the repeat count and result in a defective gene. When the length of this repeated section reaches a certain threshold, it produces an altered form of the protein, called mutant Huntingtin protein (mHTT).

HUNTINGTIN GENE (HTT)

Repeat count Classification Disease status Risk to offspring <26 Normal Will not be affected None 27–35 Intermediate Elevated but <<50% 36–39 Reduced Penetrance May or may not be affected 50% 40+ Full Penetrance Will be affected

Treatment for Huntington's disease There is no current treatment that halts or even slows the disease's progression. Huntington's disease is incurable. There is no current treatment that can reverse its progression or slow it down. Scientists at UT Southwestern Medical Center found that man- made molecules that selectively interfere with protein production can stop human cells from making the abnormal moleculesthat cause Huntington's disease. They added that "The work has been done only in cultured cells, and it will take years before the effectiveness of this process can be tested in patients."

Huntington's disease is incurable Huntington's disease is incurable. There is no current treatment that can reverse its progression or slow it down. Scientists at UT Southwestern Medical Center found man-made molecules that selectively interfere with protein production which stop human cells from making the abnormal molecules that cause Huntington's disease. They added that "The work has been done only in cultured cells, and it will take years before the effectiveness of this process can be tested in patients."

Medications Tetrabenazine (Xenazine) - in August 2006 the FDA (Food and Drug Administration), USA approved tetrabenazine for the treatment of jerky, involuntary movements (chorea) associated with Huntington's disease - the first to be specifically approved for this in the country. The compound has been known since the 1950s. It promotes the early metabolic degradation of the neurotransmitter dopamine. Deutetrabenazine (Austedo) - an isotopic isomer of tetrabenazine in which six hydrogen atoms have been replaced by deuterium atoms which slows the rate of drug metabolism. Approved by FDA in 2017. Speech therapy Speech therapy can help patients find strategies to utter words and phrases and communicate in a more effective way. Physical and Occupational therapy Better muscle strength and flexibility can be achieved with a good physical therapist. Strength and flexibility will help the patient's balance and reduce the risk of falling. An occupational therapist can help the patient devise strategies for coping with concentration and memory problems, as well as making the home safe

Approved Uses Important Safety Information AUSTEDO® is a prescription medicine that is used to treat: the involuntary movements (chorea) of Huntington’s disease. AUSTEDO® does not cure the cause of the involuntary movements, and it does not treat other symptoms of Huntington’s disease, such as problems with thinking or emotions. movements in the face, tongue, or other body parts that cannot be controlled (tardive dyskinesia). It is not known if AUSTEDO® is safe and effective in children. Important Safety Information AUSTEDO® can cause serious side effects in people with Huntington’s disease, including: depression, suicidal thoughts, or suicidal actions. Do not start taking AUSTEDO® if you are depressed (have untreated depression or depression that is not well controlled by medicine) or have suicidal thoughts. Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts or feelings. This is especially important when AUSTEDO® is started and when the dose is changed. Call your healthcare provider right away if you become depressed, have unusual changes in mood or behavior, or have thoughts of suicide.

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