Spinocerebellar ataxia type 1


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  • How would you feel if you slowly lost the ability to walk? How would you feel if you couldn’t talk? How would you feel if you couldn’t eat or even catch a ball? Well today we will be presenting you with a disease called SCA. The people affected with this disease have to deal with these problems and even more every single day.
  • Point 3- may affect your muscles temp. or permantly.
  • Purr-kin-g
  • What is ATNX1? Is there supposed to be an H? Is the ATNX1 the allele?
  • Don’t say last two points. And “scientists do not know what Ataxin-1 does yet, but we do know that it causes shrinking of the cerebellum and death of Purkinje cells.”
  • Draw punnet square on board when mia is talking LEFTTTT ARRRMMM BELOW Centro MERE!!!
  • Stem cells are unique because they are able to change into all different types of cells such as mucsles, tissue, nerve.---- People with SCA lose many dopamine-producing cells, and this is a problem because dopamine is a neurotransmitter which send messages that coordinate movement to the brain. Scientists hope to use stem cells to replace those.
  • Pathology- course of descruction of purkinje
    Histopatholgy- structire of abnormal or dead tissue
  • Spinocerebellar ataxia type 1

    1. 1. Biology Amelia Gelz Tina Ma Michele Zhang Tina Dhaliwal
    2. 2.  What is ataxia?  What is spinocerebellar ataxia?  What are the genetics of spinocerebellar ataxia?  Genes and chromosomes that affected  Inheritance  Pedigree of a family with spinocerebellar ataxia  How is it diagnosed?  Symptoms and onset of symptoms  How is it diagonosed?  What is the prognosis?  Therapy and treatment  Hope for the future
    3. 3.  Ataxia is not a specific disease or diagnosis  Ataxia is a word used to describe certain symptoms related to movement, such as:  Unsteady walking  Difficulty with balance  Loss of coordination  Slurred speech  Ataxia may be temporary or progressive and permanent  Spinocerebellar ataxia is one form of permanent ataxia
    4. 4.  Spinocerebellar ataxia (SCA) is a rare genetic disease that affects the cerebellum, brain stem and spinal cord  There are 29 different types of SCA  These 29 types are linked by common causes and symptoms, but they each have acquired symptoms unique to that type  Out of these 29 types, SCA1 is one of the most common along with SCA2 and SCA6
    5. 5.  SCA1 affects the cerebellum located near the back of the brain  The cerebellum is the region of the brain that is involved in:  Motor control  Balance and equilibrium  The precision, timing and coordination of movements  The cerebellum is actually a continuous layer of neural tissue  An important layer of the cerebellum is the Purkinje Layer, where Purkinje cells control the output of all motor coordination
    6. 6.  The cerebellum gradually deteriorates due to a harmful mutation  The loss of Purkinje cells in the cerebellum causes a loss of balance and coordination  This leads to SCA1  Above: 2 MRI scans of a man with a normal cerebellum and a man with spinocerebellar ataxia
    7. 7.  Above: the ataxin-1 protein  SCA1 is caused by the ATNX1 gene mutation on chromosome 6  A sequence of 3 bases, CAG, are replicated many times  This causes an excessive production of the ataxin-1 protein, which causes SCA1  The diseased allele can contain between 41-81 CAG repeats where normally there would only be 6-39 repeats  The longer the expansion, the more severe the disease becomes
    8. 8.  Although the exact function of ataxin-1 is unknown, scientists do know that:  Ataxin-1 is attracted to certain parts of the cerebellum and eventually will destroy the layers, causing atrophy (shrinking) of the cerebellum  A toxic buildup of ataxin-1 causes damage to the cerebellum Purkinje cells, which blocks messages to the brain concerning motor coordination  The polyglutamine expansions often vary in size and are very unstable  They usually increase in size which is passed onto successive generations
    9. 9.  SCA1 is passed on through autosomal dominant inheritance  This means both affected parents have a 50% chance of passing on the mutated gene  However, if the CAG triplets in the offspring repeats in a normal range, the child might not have the disease  Every 1 in 100,000 people will suffer from SCA1
    10. 10. Above is a pedigree of a family with SCA1. This shows autosomal dominant inheritance with one of the females diagnosed with SCA1.
    11. 11.  Early symptoms:  Walking, balance and coordination problems (gait difficulty)  Precision, timing and coordination of movements significantly decreases  Later symptoms:  Difficulty swallowing (dysarthria)  Difficulty judging the distance between objects (dysmetria)  Neuropathy (loss of feeling and reflexes in legs and feet)  Spasticity
    12. 12.  In SCA1, the number of CAG repeats determined 64% of onset variability  From the onset of the symptoms, the duration of SCA1 is from 10 to 30 years  The onset of symptoms usually appear in adulthood (ranging from 20’s to late 30’s)  If the onset of symptoms appear before the age of 13, the disease is usually much more severe and the progression more rapid
    13. 13.  How is it diagnosed?  A neurological examination is conducted and will determine whether an individual has symptoms typical of SCA1  A blood test is conducted to detect the abnormal gene  DNA tests to analyze any gene mutations on the 6th chromosome  MRI scan of the brain
    14. 14.  Unfortunately there is no cure for SCA1  The loss of muscle control will worsen until the patient cannot eat or breathe  Scientists have not yet found a way to prevent neurons from dying a premature cell death  Scientists have also not found a way to restore neuronal populations that have already been lost
    15. 15.  However a number of different therapies are available to help affected individuals cope their disease:  Physical therapy  Speech therapy  Emotional therapy and support  Conveniences:  Installing grab bars, ramps and raised toilets at home  Canes, crutches, walkers and wheelchairs to help walking  Computer communication devices  Weighted eating tools
    16. 16.  Stem cells are cells found in all multi-cellular organisms and can change into a wide range of specialized cell types  Stem cell tissues can be cultured into cells with the characteristics of the cells of tissues, muscles and nerves  In adults, stem cells can act as a repair system replenishing specialized cells  The goal is to coax stem cells to become nerve cells to replace dopamine-producing cells that have been lost in the brain
    17. 17.  The Institute of Clinical Neurosciences at the University of Bristol conducted a study on the use of bone marrow stem cells to treat degenerative ataxias  To test this theory, cerebellar cells were taken from rodents, grown in a culture and subjected to toxins  The effect of stem cells on the survival of the nerve cells was tested and scientists discovered:  Nerve cells in the presence of the human bone marrow derived stem cells were less likely to die  These stem cells are able to protect nerve cells that have been exposed to toxins
    18. 18.  Stem cell research is currently more advanced in China than in North American due to ethical issues  George Arruda was diagnosed with SCA1 and flew to China to receive stem cell injections that could potentially improve his condition  George experience significant improvements in his walking, balancing and coordination after the injections
    19. 19.  A study performed in 2005 showed that SCA1 pathology in transgenic mice can be reversed  The gene for ataxin-1 (ATNX1) was put into a tetracycline-sensitive promoter  The administration of doxycycline (tetracycline) was discovered to have the ability to shut off the activated gene  Transgenic mice were given doxycycline varying from 6, 12, 16 or 32 weeks and the general results were:  6 weeks: Purkinje cell pathology was reversed  12 weeks: Restored motor function  32 weeks: Significant improvements in histopathology
    20. 20.  The National Institute of Neurological Disorders and Stroke are currently testing the use of the drug lithium carbonate  Lithium injections have been tested on mice diagnosed with SCA1 and have shown neurological improvement  The University of South Florida is testing the use of the drug varenicline (a drug used to smoking cessation) and the drug placebo  Varenicline has shown substantial improvement in patients with several inherited ataxias  These drugs are targeted towards SCA3 but because all types of SCA are linked by common symptoms, this may also provide helpful research in the treatment of SCA1
    21. 21.  Aya Kito was born on July 19, 1962 in Japan  At the age of fifteen she was diagnosed with spinocerebellar ataxia type 1  She slowly lost her ability to walk and talk and spent the rest of her life in a hospital bed  Aya wrote a diary documenting her personal experiences with spinocerebellar ataxia  Her diary was published on February 25th, 1986 and was titled 1 Litre of Tears  Aya Kito died on May 23rd 1988
    22. 22.  http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene &part=sca1  http://www.ataxia.org/pdf/NAF%20Web%20Content%20Pub lication%20SCA1.pdf  http://clinicaltrials.gov/ct2/show/NCT00683943?term=spi nocerebellar+ataxia+1&rank=2  http://www.mdvu.org/emove/article.asp?ID=788  http://www.medicalnewstoday.com/articles/29733.php  http://stemcellschina.net/  http://myweb.tiscali.co.uk/ataxia.pages/index.htm#ATAXI APAGE-Understanding_Genes  http://www.ataxia.org.uk/publications_and_pictures/Deg enerative%20ataxias%20and%20the%20potential%20for%20st em%20cell%20neuroprotection.pdf  http://www.uniprot.org/uniprot/P54253