1. STEM CELL RESEARCH ON HUNTINGTON’S DISEASE Josh Merrifield, Michael Jennings, and Stephanie Antone

2. WHAT IS HUNTINGTON’S DISEASE? Medium Spiny Neurons (MSNs) Function: coordinating information from other neurons in the brain to control movement of the body, face, and eyes. Production of toxic version the Huntington protein. Alters DNA sequence (CAG). Children with affected parents have a 50% chance of inheriting Huntington’s Disease. Symptoms begin to occur around 35-50 years of age. Weak spasms of muscles in the face and limbs. Aging makes the spasms more prominent. Patients may be affected in different ways… trouble swallowing, speaking, and dementia. Affects nerve cells in the brain Large numbers of MSNs are damaged and destroyed. Ex.. Cortical neurons or destroyed in the brain and the nerve endings are severed and damaged. MSNs and other neurons are lost for coordinating muscle movement.

3. TREATMENTS No effective treatments have been discovered at the time being. Therapies manage symptoms by controlling movements. Tetrabenazine, benzodiazepines, and antipsycotics are used for treatment drugs. Drugs are used to help with hyperkinetic movements and spasms. VMAT2: a protein that is encoded by SLC18A2 gene. Function: to help transport monoamines such as neurotransmitters (dopamine, norepinephrine, serotonin, and histamine from the cytosol into synaptic vesicles. Speech therapy is also used

4. TESTS FOR HUNTINGTON’S DISEASE While there are no cures for Huntington’s disease, there are tests that allow people to know if they have the disease. Since Huntington’s Disease can be an early onset and an adult onset disease, there are adult tests, prenatal tests and preimplantation tests. Testing is important for the disease, because even though there are no cures currently, it is good to know so that stem cell transplants can be tried to help cure the disease. There are neurological and neuropsychological examinations, brain imagining tests, and predictive genetic tests for adults and others for prenatal and preimplantation testing.

5. NEUROLOGICAL, NEUROPSYCHOLOGICAL AND BRAIN IMAGING TESTS In these tests, the doctor will test motor and sensory reflexes that may develop. Huntington’s causes the deteriorated ability to move and the loss of sensation. Doctors will also determine the mental status of the patient. Many patients experience depression, a dulled sense of judgment and mental agility, and disordered thinking. Many Huntington’s patients will have to take brain imaging tests through MRI’s so that the doctor can see the progression of the atrophy due to the disease in the actual brain.

6. FOR ADULTS, THERE ARE ALSO GENETIC TESTS There are predictive genetic tests that allow patients to know if they carry the genes for the disease. Disease is autosomal dominant that could be passed by mothers or fathers which can effect males and females. If a mother or father possesses the gene, it is likely that it will be passed. The disease is a mutation on the HTT gene on the 4 th chromosome and the predictive genetic test will be able to identify the mutation on this gene.

7. PRENATAL AND PRE- IMPLANTATION TESTS. Prenatal testing – when one parent is diagnosed with the disease, the cells of a developing fetus can be tested with chorionic villi sampling or amniocentesis. If the parents see that their child has the disease, some of them choose to terminate the pregnancy. Pre-implantation tests are also available for people who are carriers for the disease who do no show symptoms. These tests can be done in vitro to determine which embryos have the CAG genes.

8. STEM CELL RESEARCH ON HD Stem cells are used to grow large numbers of cells in a laboratory. MSNs can be regrown by stems cells and researchers are able to study the functions of the neurons. These stem cells can replace the damaged neurons in the brain but more research is needed in order to produce viable results on human subjects. Short term improvements in patients have led researchers on an optimistic understanding on how to cure HD permanently. Researchers hope to use embryonic stem cells in order to produce unlimited sources for MSNs.

9. STEM CELL RESEARCH CONTD’ MSN deterioration is thought to be the main cause of HD however, other neurons are affected and can produce neuron deterioration. Lab-grown stem cells are examined and duplicated in order to help researchers understand their function and correctly depict their influence of the physiological effect of MSNs synapses. Replacing lost cells has ultimately helped patients with early onset of HD however, as the years go on, the same patients had reoccurring symptoms. Although embryonic stem cells are though to be the main source of a curable outcome, pluripotent may have the same effect. More research is needed in this field.

10. STEM CELL USE ON RODENTS WITH INDUCED HD Rodent have been injected with embryonic stem cells In some cases, rodents have improved and the lab – grown stem cells have been view to hold key properties A rodents brain may be similar but capabilities of their brain are limited A human brain is much more intricate.

11. HD and genes: Hungtinton's disease patients have a Huntingtin gene containing too many copies of a DNA sequence known as 'CAG repeats'.

12. STEM CELL RESEARCH TODAY Recent studies show that stems cells are effective but there is a long way to go for viable results. More studies must be conducted in order for carriers to be cured. Transplants of lab – grown stem cells must be able to proved identical functions to the human brain before further implementation can occur. Stem cells cannot be used today due to unanswered question to how long the human brain can effectively use them. The body may counteract the stems cells and ultimately severely damage the brain by toxic pluripotent cells.

13. REFERENCES http://www.eurostemcell.org/factsheet/huntington%E2%80%99s-disease- how-could-stem-cells-help http://www.eurostemcell.org/factsheet/huntington%E2%80%99s-disease- how-could-stem-cells-help http://www.mayoclinic.org/diseases-conditions/huntingtons- disease/basics/tests-diagnosis/con-20030685 http://www.mayoclinic.org/diseases-conditions/huntingtons- disease/basics/tests-diagnosis/con-20030685 http://www.hdfoundation.org/html/hdsatest.php http://www.eurostemcell.org/factsheet/huntington%E2%80%99s-disease- how-could-stem-cells-help http://www.eurostemcell.org/factsheet/huntington%E2%80%99s-disease- how-could-stem-cells-help http://www.ucdmc.ucdavis.edu/stemcellresearch/research/huntingtons- disease.html http://www.ucdmc.ucdavis.edu/stemcellresearch/research/huntingtons- disease.html http://www.nature.com/ejhg/journal/v10/n10/full/5200865a.html http://www.ncbi.nlm.nih.gov/pubmed/12357329