RESEARCH PROFILES

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The Role of Purines in the Repair of Damaged Nerves

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By Anita Shama
Canadian Spinal Research Organization

After a spinal cord injury, damaged cells release large quantities of chemicals called purines.

Purines make up part of the basic components of genetic material (ex. DNA), as well as act as the energy currency of cells. There are two types of purines, adenosine and guanosine, which also play important roles outside cells. They signal nerve cells to protect themselves from further damage, and also act as chemical messengers to signal cells called astrocytes and glia to release trophic factors. Glia and astrocytes are supporting cells in the central nervous system (CNS), and the trophic factors that they secrete aid in the repair of damaged nerves. Unfortunately, the purines released from injured cells do not accumulate to large enough amounts to have significant effects. Thus, a synthetic purine has been created to supplement those naturally occurring. This synthetic purine, also known as AIT-082, is a derivative of guanosine. AIT-082 is active when orally ingested, so there may be a potential drug use.

In addition to the effects already mentioned, guanosine and AIT-082 also stimulate the release of adenosine by astrocytes. Thus, adenosine release occurs from both the initial damaged cells, as well as being induced by guanosine and its derivative. The only problem is that the release of large quantities of adenosine by injured or dying cells seems to reach local concentrations high enough to signal apoptosis, a genetically programmed cell death. This process occurs via a receptor on the cell surface of the astrocytes, called the A3 receptor. Apoptosis of the astrocytes results in the loss of the neurons they support. Blocking the A3 receptor could prevent the inappropriate signaling of apoptosis by adenosine, yet allow the positive circulatory and trophic effects signaled through two other adenosine receptors.

Dr. Michel Rathbone talks about Purines.

Treatment of SCI rats with AIT-082 resulted in less swelling and necrosis (cell death resulting from trauma) of their spine. A downside to the usage of AIT-082 is that it negatively interacts with a drug called methylprednisolone, which is initially administered in high amounts after spinal cord injuries. Preliminary tests are being conducted to determine the methods of administration that will maximize the potential use of these two drugs in the future.