Bonus Evidence –Enzyme Therapy on the Authentic Mouse Model

History:

* What isTay 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 these10test micedaily with the HEXA enzyme
  3. They used10mice as the control for their experiment. These mice werenot given the enzyme HEXA.
  4. They monitored how their nerve cells reacted to muscle stimulation.

Results:

  1. After 18 days, the10controlmice died due to starvation.
  2. Why did they starve?The 10 mice that were notgiven theenzyme 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. The10 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.