Wednesday, 4 April 2012

Muscular Gene Therapy- Applications

Gene therapy is the application of DNA as a pharmaceutical product to treat medical conditions.[3] It has become extremely popular in medical research throughout the last 10 years and a number of researchers have focused on the rehabilitation of muscle strength, endurance and size. There has been amazing potential for the elderly and sufferers of muscle deteriorating diseases such as muscular dystrophy.[5]
The genes that are involved in my research of the topic include:
1.   IGF-I: which regulates the multiplication of satellite cells in muscles
2. Myostatin: regulates the ‘stop’ point of IGF-I – so when satellite cells have multiplied enough,  myostatin is produced, and IGF-I synthesis is stopped
3. PPARδ: involved in metabolic functions of muscles and, for simplicity, the endurance of muscles
Before explaining gene therapy, I’ll let you know what satellite cells are to aid your understanding. Satellite cells are found in mature muscle between individual muscle fibres and when the muscle is damaged, for example through exercise, the satellite cells divide and differentiate to become the new muscle fibres.
In terms of gene therapy and muscle repair, researchers have found that they can change the chemical signals normally involved muscle repair by inserting the IGF-I genes mentioned earlier. One experiment found that a synthetic gene of IGF-I has the potential to alter muscle functioning to create bigger stronger muscles.[5] In a normal functioning muscle, natural IGF-I would initiate satellite cells to multiply and the corresponding gene myostatin would signal the division to stop when enough have been produced. However when the synthetic IGF-I gene is inserted into the cell via a vector, it would block myostatin from communicating with satellite cells.[1] Therefore more are produced and a larger, stronger muscle is formed due to an overload of muscle fibre.
In a study on mice, this exact method occurred, and what resulted was a mouse with visibly larger muscle size and therefore increased strength. The picture here demonstrates the increase in muscle size of the mice.[1]

Through the same method of injecting genes via a vector, other genes can be used for production within cells to aid frailty and disease. The next gene, PPARδ, is involved in endurance. Within a muscle there are two types of muscle fibres.[4] The difference between the two muscle fibres is, the first fast contracting muscle fibres, are for speed of muscle contractions. The other, slow contracting muscle fibres are for endurance. When the PPARδ gene is synthesised within cells, it converts the fast fibres to slow fibres allowing the muscles to continue contracting for longer periods of time.[2] Thus resulting in greater endurance. Just to show how effective this gene is, think about the next experiment.
An investigation of the PPARδ gene showed that, when injected into mice, the animals muscle fibres contracted for longer periods of time. So much so that the test subject could run an average of 92% longer in distance with a 67% improvement of time over the control mouse.[1]
Therefore it is quite visible how much of an improvement these genes could harbour if injected into humans with debilitating diseases or frailty in old age.

BELGIAN BLUE BULL demonstrates the effect of blocking the antigrowth factor myostatin. The absence of myostatin also interferes with fat deposition, making these “double-muscled” cattle exceptionally lean.

Reference List:
1. Azzazy, H. Christenson, R. Mansour, M 2009, ‘Gene Doping: Of mice and men’, Clinical Biochemistry, vol. 42, issue 6, pp. 435-441
2. Baoutina, A. Alexander, IE. Rasko, JE. Emslie, KR 2007, ‘Potential use of gene transfer in athletic performance enhancement’, Mol Ther, vol. 15, pp. 1751–1766
3. Gene Therapy 2012. Encyclopædia Britannica Online. Retrieved 21 March, 2012, from
4. Grimaldi, P.A 2005, ‘Regulatory role of peroxisome proliferator-activated receptor delta (PPAR delta) in muscle metabolism’, Biochimie, vol. 87, pp. 5–8
5. Sweeney, H 2004, ‘Gene Doping’, Scientific American, vol. 291, issue 1, pp. 62-69

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