Evidence 4 – Enzyme Therapy on the Authentic Mouse Model
History:
* What is Tay Sachs Disease? It is genetic disorder caused by the
absence of a specific enzyme called beta-hexosaminidase (HEXA).
* What is HEXA? It is an enzyme that plays a critical role in breaking
down and recycling fatty substances that build up within the body.
* Why does Tay Sachs occur? There is usually a problem or mutation with the HEXA gene.
The HEXA gene makes a protein that forms the enzyme HEXA.
* What problem does this cause? Without the gene functioning properly, it cannot produce
the enzyme that breaks down fats. These fats then build up in toxic levels leading to
destruction and results in damage to the brain and nerve cells.
* What is the result? Most often Tay Sachs results in paralysis and eventually death.
Introduction: Doctors at the Canadian Institute of Health Research and Genetic Diseases were
seeing a rise in the number of patients coming in and being diagnosed with Tay Sachs disease.
Understanding that the disease is very powerful and almost always results in death, they became
even more anxious to try and find a cure. The doctors and researches that were affiliated or
worked with the Institute decided to investigate a mouse model. They wanted to find out: If they
administered the enzyme (HEXA) to affected mice (mice with Tay Sachs), could they avoid
paralysis?
Method:
1. The researchers and doctors of the Canadian Institute of Health Research and Genetic
Diseases took a group of 20 mice that tested positive for the malfunction in the HEXA
gene.
2. They used 10 of the mice as test (experimental) subjects. The scientists injected these
10 test mice daily with the HEXA enzyme
3. They used 10 mice as the control for their experiment. These mice were not given the
enzyme HEXA.
4. They monitored how their nerve cells reacted to muscle stimulation.
Cachón-González, M. B., Wang, S. Z., Lynch, A., Ziegler, R., Cheng, S. H., & Cox, T. M. (2006). Effective
Gene Therapy in an Authentic Model of Tay-Sachs-Related Diseases. Proceedings of the National
Academy of Sciences of the United States of America, (27). 10373.
Results:
1. After 18 days, the 10 control mice died due to starvation.
2. Why did they starve? The 10 mice that were not given the enzyme HEXA (control)
lost so much muscle movement due to
the damage of the nerve cell they could
not feed or water themselves (mouse B).
3. The 10 experimental mice (mouse A)
that were given the synthetic HEXA enzyme showed a slower progression of nerve
damage and no little muscle degeneration.
The HEXA mice ended up living four times longer (72 days) than the control mice. After the
experimental mice died the nerves in their brains were analyzed to see how the synthetic enzyme
HEXA had affected the progression of the Tay Sachs diagnosis. When the HEXA enzyme was
present the Tay Sachs symptoms resulted in no muscle paralysis.
1. What can you conclude about the way neurons communicate with the muscles? Draw your
conclusion from the study above. (In other words, do neurons communicate with muscles? If yes,
how do you know this from the study?)
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2. Did the enzyme HEXA help avoid paralysis? If yes, how did it help avoid paralysis?
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Cachón-González, M. B., Wang, S. Z., Lynch, A., Ziegler, R., Cheng, S. H., & Cox, T. M. (2006). Effective
Gene Therapy in an Authentic Model of Tay-Sachs-Related Diseases. Proceedings of the National
Academy of Sciences of the United States of America, (27). 10373.