SRF – GlycoSENS

Summary

Much of the structural features of the body are made of proteins that are created early in life. These structures are either not replaced or recycled, or if they are, they are at a very slow rate over decades. The health of these structural components relies on the proteins making them up retaining their proper structure.

These proteins are responsible for the elasticity of tissue, such as in the skin and blood vessel walls, as well as the transparency of the lens of the eye. Unfortunately, blood sugar and other molecules react with these structural proteins and bond with them, creating fused crosslinks. Crosslinks bind neighboring proteins together impairing their movement and function. In the case of the artery wall, crosslinked collagen prevents the artery from flexing in time with the pulse, leading to hypertension and a rise in blood pressure.

This loss of flexibility increases over time, meaning the full force of blood being pumped around the body goes directly into the organs, damaging them instead of being absorbed by the blood vessel walls. In time this leads to organ damage and an increase in the risk of stroke. The most numerous crosslink by a huge margin in humans is glucosepane and is, therefore, the one that attracts the most interest from researchers in the field.

The SENS Research Foundation proposes to find ways to break down these glucosepane crosslinks to restore movement to the structural proteins, and thus reversing the consequences of their formation. There are a number of types of crosslinks that accumulate in the body, but the focus is on glucosepane, which is a very long lasting crosslink that the body can only break down very slowly if at all.

One of the problems with finding ways to breakdown glucosepane was obtaining it in large quantities in order to test potential breakers on. This issue was solved in 2015 when the total synthesis of glucosepane was perfected by Professor David A. Spiegel, Ph.D., M.D. and his team at Yale University. Thanks to the funding from the SENS Research Foundation, progress at Yale University now allows for the cost-effective production of glucosepane on demand, which means that researchers can now test directly on it and find antibodies and enzymes to dissolve the accumulated crosslinks.

Yale already has some antibodies against glucosepane; it is anticipated that, by the end of the year, monoclonal antibodies will be available, and there is strong evidence for bacteria with enzymes that can break down glucosepane.

References

[1] Draghici, C., Wang, T., & Spiegel, D. A. (2015). Concise total synthesis of glucosepane. Science, 350(6258), 294-298.

Website: The SENS Research Foundation, Yale University,  Spiegel Research Group