We are pleased to hear that the SENS Research Foundation has announced a new research program in collaboration with the Spiegel lab at Yale University. This new project is a continuation of their joint efforts regarding the crosslink glucosepane and sees them moving towards effective ways to remove it from the body to address age-related diseases.
Today, we will take a quick look at what crosslinks are, how they contribute to age-related diseases, and what the SENS Research Foundation proposes to do about them.
What are glucosepane crosslinks?
One suspected reason we age is the accumulation of sugary metabolic wastes known as advanced glycation end-products (AGEs). AGEs are wastes that are, in some cases, hard for our metabolisms to break down quickly enough or even at all.
There are various kinds of AGEs present in the body, although none are as common as glucosepane, which is the most abundant by a huge margin. Glucosepane is very hard for the body to break down (if indeed it can at all), and it can last several decades once formed.
AGEs, such as glucosepane, form cross-links, binding together important proteins such as those making up the supporting extracellular matrix scaffold and preventing them from moving.
The elastic properties of skin and blood vessel walls are due to the extracellular matrix having a particular structure, and cross-links degrade that structure, preventing it from functioning correctly. The presence of AGEs contributes to blood vessel stiffening with age and is implicated in hypertension and diabetes [1-2].
The SENS solution to dealing with AGEs would be to find ways to break down the crosslinks, thus freeing up the trapped proteins and restoring tissue elasticity.
A major hurdle is overcome
Until recently, glucosepane was very difficult to isolate in order to test drugs and therapies on. This changed in 2015 when, thanks to funding from the SENS Research Foundation, the Spiegel lab was able to create glucosepane on demand .
This means that the lab now has a cost-effective way to create glucosepane and can begin to develop therapies to remove it from the tissue. Therefore, the lab is now developing the first monoclonal anti-glucosepane antibodies as the next step towards developing glucosepane-cleaving therapies.
A monoclonal antibody is a type of lab-created protein that is designed to bind to only one substance. Such an antibody can be used alone or to carry drugs directly to target cells and tissues.
The creation of monoclonal anti-glucosepane antibodies has huge implications for how we treat age-related diseases, so we are delighted to hear the news of this research project. We interviewed Dr. Aubrey de Grey from the SENS Research Foundation earlier this year, and the progress with glucosepane breakers was mentioned at the time; it is great to see that this work is now moving forward as planned.
SRF and Spiegel Lab to Collaborate on Antibodies to Glucosepane
SENS RESEARCH FOUNDATION ANNOUNCES NEW RESEARCH PROGRAM ON DEVELOPING MONOCLONAL ANTIBODIES AGAINST GLUCOSEPANE WITH DAVID SPIEGEL LAB
MOUNTAIN VIEW, Calif.— September 18, 2017 — SENS Research Foundation (SRF) has launched a new research program focused on developing monoclonal antibodies against glucosepane. David A. Spiegel, MD, PhD is Professor of Chemistry and Pharmacology at Yale University, and will be running the project in his laboratory, which focuses on developing new methods and molecules that will facilitate our understanding and treatment of human disease.
Glucosepane is the most prevalent crosslink found in collagen in people over 65 years of age, and its presence has been correlated to age-related tissue damage through various mechanisms. Understanding of glucosepane has been hampered by the molecule’s complex and sensitive chemical structure; it can only be isolated from human samples in minute quantities and in an impure form.
To enable these advances in both basic and therapeutic science, the Spiegel laboratory has recently accomplished the first total synthesis of glucosepane.
The lab is now utilizing its novel synthetic glucosepane derivatives to generate the first monoclonal anti-glucosepane antibodies. Access to these antibodies would profoundly enable and accelerate the goal of developing the first anti-glucosepane monoclonal antibodies, while consequently bringing closer the obtainment of the first discrete, specific reagents for labeling, studying, and perhaps also cleaving glucosepane in vivo. Such tools have tremendous potential to help illuminate, and reverse, age-related damage as it occurs in human tissues.
“Our collaboration with SRF has significantly increased our understanding of glucosepane and the impact it has on our tissues as we age. I am very pleased to continue collaborating with SENS Research Foundation,” said Dr. Spiegel.
“Launching our new project with David Spiegel will enable SRF to continue to build on the momentum which was created by his initial project which resulted in his ability to synthesize glucosepane. Now we are able to move forward in the creation of potential treatments for age-related damage in human tissue,” said Dr. Aubrey de Grey, CSO, SENS Research Foundation.
This research has been made possible through the generous support of Michael Antonov and the Forever Healthy Foundation and its founder Michael Greve. The Forever Healthy Foundation is a private nonprofit initiative whose mission is to enable people to vastly extend their healthy lifespans and be part of the first generation to cure aging. In order to accelerate the development of therapies to bring aging under full medical control, the Forever Healthy Foundation directly supports cutting-edge research aimed at the molecular and cellular repair of damage caused by the aging process.
About SENS Research Foundation (SRF)
SENS Research Foundation is a 501(c)(3) nonprofit that works to research, develop, and promote comprehensive regenerative medicine solutions for the diseases of aging. SRF is focused on a damage repair paradigm for treating the diseases of aging, which it advances through scientific research, advocacy, and education. SENS Research Foundation supports research projects at universities and institutes around the world with the goal of curing such age-related diseases as macular degeneration, heart disease, cancer, and Alzheimer’s disease. Educating the public and training researchers to support a growing regenerative medicine field are also major endeavors of the organization that are being accomplished though advocacy campaigns and educational programs. For more information, visit www.sens.org.
 Genuth, S., Sun, W., Cleary, P., Gao, X., Sell, D. R., Lachin, J., … & DCCT/EDIC Research Group. (2014). Skin advanced glycation endproducts (AGEs) glucosepane and methylglyoxal hydroimidazolone are independently associated with long-term microvascular complication progression of type i diabetes. Diabetes, DB_140215.
 Monnier, V. M., Sun, W., Sell, D. R., Fan, X., Nemet, I., & Genuth, S. (2014). Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications. Clinical chemistry and laboratory medicine, 52(1), 21-32.
 Draghici, C., Wang, T., & Spiegel, D. A. (2015). Concise total synthesis of glucosepane. Science, 350(6258), 294-298.