Huntington s disease

Biology 103 Lab Presentation Zachary Dequilla, Kathleen Pellegrino, Rachel Weinstein, Travis Hawkins

Case Study
Bryan is in his mid 30s and just got back from his annual physical check up at the doctor. While he doesn t feel sick, the doctor told him that he might have a condition called Huntington s disease and scheduled him for an appointment the following week with a specialist to discuss the issues and do some follow up tests. Bryan hadn t even heard of the disease before the visit to the doctor, but now it is all he can think about. He is worried if it is fatal, how long he has to live. Will his kids inherit it? Will he be a burden on his wife, and many other questions.

introduction
- Huntington s disease, is a chronic, progressive, hereditary, and familial disease characterized by bizarre movements, speech disturbances, and mental deterioration that gradually leads to dementia - It is a neurodegenerative condition that afflicts about 30,000 people in the United States alone. - Autosomal dominant, transmitted by both sexes - Each child of an afflicted parent has a 50% chance of inheritance.

heredity

symptoms
- Symptoms usually appear between ages 30 to 40 - Impaired problem-solving, concept formation, verbal storage, alertness, and concentration - Progressive Mental Deterioration - impulsive behavior, which may cause social problems - The person becomes dependent - Difficulty in thinking and communicating interferes with expressing needs and fears - Emotional disturbances

symptoms
- Paranoia, delusions, grandiose ideas, and hallucinations depressed states with suicidal tendencies - Involuntary movements - The disease itself isn t fatal

Locating the disease

- In 1979, the Hereditary Disease Foundation found a restriction enzyme marker showing close genetic linkage to Huntington s chorea is on chromosome 4 - A large number of persons at risk will be able to learn whether or not they will get it - It is also possible that the disease is caused by a collection of genes

Limitations in locating the Huntington's disease gene

- I=2M/1-F isn t a reliable formula - There might be more than one genetic locus, and if so, the precise distance between them would be hard to determine - There isn t enough protein markers in Huntington s

Brains in Huntington's patients

Normal brain

Huntington s Patient

Nucleus Deficiencies
- Nucleotides: C, A, and G repeat in DNA - Deficiency in GABA and acetylcholine - Excess of dopamine in relation to acetylcholine and GABA Possible treatment

Care plan for Huntington s

I. Admission - Vital signs - Weight - Skin Condition - Anxiety - Motor Activity
II. Complications due to Progression - Difficulty in ambulation - Difficulty in swallowing - Increase in involuntary movements - Urinary Incontinence - Fecal impaction - Persistent weight loss - Depression - Suicidal Intent - Aspiration Pneumonia III. Preparation for Discharge - General Health - Activity - Progression of Disease - Hereditary aspects - Medicine - Follow-up Care

Huntingtin mutations
- Huntingtin (Htt) malfunctions and kills neurons when mutated - Htt disrupts nerve cell function = neuronal death - The mutations causing the disease occur near the beginning of a gene, in a segment that codes for a repeating string of the amino acid glutamine - Normal Htt: 6 35 glutamines - Mutated Htt: 36+ - Abnormal deposits of the mutant Htt fragments is found

Pharmalogical treatments
Drug Coenzyme Q10 Creatine Cystamine Geldanamycin HDAC inhibitors Memantine Minocycline Paroxetine Rapamycin Actions Antioxidant, protects mitochondria Stabilizes mitochondria Decreases Htt aggregation Decreases Htt aggregation Counters Htt transcription effects Neurotransmission Decreases cell death, Htt aggregation Protects neurons by increasing BDNF Decreases Htt aggregation by stimulating autophagy Status in Huntington s Late Clinical Trials Early Clinical Trials Early Clinical Trials Preclinical Early Clinical Trials Early Clinical Trials Early clinical trials Preclinical Preclinical

Rapamycin
- Suppresses Htt aggregate formation and decreases related toxicity in neurons - Enhances autophagy cells use to destroy excess or damaged proteins - Autophagy can t keep mutant Htt in check forever - Treatment must be Preclinical

p53
- Mutant Htt binds to a transcription factor called p53, which controls several genes, including some affecting mitochondria - The increase in p53 activity that occurs when it binds mutant Htt causes an abnormal flow of calcium ions across the mitochondrial membrane, thereby disrupting function of the organelles and leading to cell death

BDNF
- Htt is part of the machinery that transports a nerve growth factor called brain-derived neurotrophic factor (BDNF) along their axons - Htt mutations = decline in BDNF

questions
What is the difference between Parkinson s Disease, Alzheimers, and Huntington s Disease?
Alzheimers
a progressive disease characterised by memory failure, disturbed language function and perception of reality. It is believed to be caused by the increased production or accumulation of a specific brain protein called beta-amyloid protein in the form of plaques that lead to nerve cell damage.

Parkinson s caused by the basal ganglia in your brain no longer producing dopamine which is the movement neurotransmitter. It causes tremors, slowed movement, stiffness, difficulty swallowing and incontinence.

Huntington s a genetic disease that causes degenerative changes to parts of the brain resulting in uncontrolled movements, loss of intellectual faculties and emotional disturbances.

references
Stipe, J., White, D., Arsdale, E. V., Huntington s Disease, The American Journal of Nursing, 79, 8. 1979, p.1428 1433. Lippincott and Wilkins Marx, J., Huntington s Research Points to Possible New Therapies, Science, New Science. 310, 5475. Oct 2005. p. 43 45. American Association for the Advancement of Science Carter, C., Evans, K., Baraitser, M., Effect of Genetic Counsling on the Prevalence of Huntington s Chorea, British Medical Journal, 286, 6361. Jan 1983, p. 281 283. BMJ Publishing Group Harper, P., Sarforazi, M., Genetic Prediction and Family Structure in Huntington s Chorea, British Medical Journal, 290, 6486, Jan 1985. p. 1929 1931, BMJ Publishing Group Kolata, G., Huntington s Disease Located, Science, New Science. 222, 4626, Nov 1983. p. 913 915. American Association for the Advancement of Science