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Some pleasant news has recently arrived: Revel Pharmaceuticals has successfully completed a seed round in order to begin developing therapeutics that target glucosepane crosslinks, which are a proposed reason why we age, develop diseases such as diabetes, and suffer from stiffened arteries and hypertension.

In the business of startups, a seed round refers to a series of related investments in which 15 or fewer investors “seed” a new company with funds, typically ranging between $50,000 to $2 million. This money is often used to support initial research and early development. Investors are typically offered equity, convertible notes, or preferred stock options in exchange for investing.

What are crosslinks?

A proposed reason why 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; they may even be impossible for us to break down at all, as our cells lack the tools to do so.

There are various 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.

These AGEs form crosslinks, 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 crosslinks degrade that structure, preventing it from functioning correctly. The presence of AGEs is thought to contribute to blood vessel stiffening with age and is implicated in hypertension and diabetes.

The SENS solution to dealing with AGEs is to find ways to break down the crosslinks, thus freeing up the trapped proteins and restoring tissue elasticity.

Finally, things are shifting up a gear

Revel Pharmaceuticals is a biotech company that has been established to develop drugs that can break harmful glucosepane crosslinks and is built on the work carried out by the Spiegel Lab at Yale over many years.

This research, funded by SENS Research Foundation, has steadily been progressing: initially, the researchers discovered how to synthesize glucosepane in order to facilitate testing, then they discovered bacterial enzymes that could break down glucosepane cross-links.

Those enzymes are now under development at the new company and will hopefully become the jumping-off point for their development into a therapy that can break down glucosepane crosslinks.

For the past 10 years, Yale Professors David Spiegel and Jason Crawford have been working on tools to enable the development of glucosepane-cleaving drugs. Kizoo Technology Capital investors say now is the time to advance this groundbreaking research toward the clinic and are leading funding of a new company, Revel Pharmaceuticals Inc., founded by Drs. David Spiegel, Jason Crawford, and Aaron Cravens. Kizoo leads the seed financing round at Revel, with Oculus co-founder Michael Antonov participating. SENS Research Foundation provided funding to the Yale GlycoSENS group for several years.

The long-lived collagen proteins that give structure to our arteries, skin, and other tissues are continuously exposed to blood sugar and other highly reactive molecules necessary for life. Occasionally, these sugar molecules will bind to collagen and form toxic crosslinks that alter the physical properties of tissues and cause inflammation. As a result, tissues slowly stiffen with aging, leading to rising systolic blood pressure, skin aging, kidney damage, and increased risk of stroke and other damage to the brain.

Perhaps the most important of these Advanced Glycation End-product (AGE) crosslinks is a molecule called glucosepane. Revel is developing therapeutics that can cleave glucosepane crosslinks thus maintaining and restoring the elasticity of blood vessels, skin, and other tissues, and preventing the terrible effects of their age-related stiffening.

The Yale group’s first major milestone – the first complete synthesis of glucosepane – was highly recognized when published in Science. Since then progress has been rapid, with development of glucosepane binding antibodies and discovery of therapeutic enzyme candidates capable of breaking up glucosepane crosslinks. Revel will build upon this progress by advancing the first GlycoSENS therapeutics into the clinic.

“This is truly a first. We are proud to help Revel open an entirely new category in repairing a significant damage of aging – crosslinking of collagen. Glucosepane crosslinks may cause not only wrinkles on your face but also lead to age-related rising blood pressure and possibly stroke.” says Frank Schueler, Managing Director of Kizoo Technology Capital.

David Spiegel, MD, PhD, Professor of Chemistry at Yale University and Revel founder says: “We are delighted to join Kizoo in building a world-class team to advance crosslink-breaking therapeutics into the clinic. These first-in-class agents have enormous potential to help patients suffering from a wide range of diseases”

“Collagen is the infrastructure of our bodies – in every tissue, supporting cellular function and health – but with aging, this critical molecular infrastructure accumulates damage. By clearing out this damage, we can restore tissue function and repair the body. Revel is one of only a few companies taking a repair-centric approach to treat diseases of aging and one day our AGE-cleaving therapeutics will undo this damage at the molecular level,” says Aaron Cravens, co-Founder of Revel Pharmaceuticals.

Conclusion

Finally, after many years, the research is now at the point at which a biotech company can be spun off to take the technology to market, which is where the real battle begins. Glucosepane breakers have been lagging behind most of the SENS categories, so to see a biotech company finally developing a product based on this research is very welcome news.

On a related note, it is great that Kizoo is once again supporting cutting-edge biotech companies that are focused on repairing the damage of aging. Kizoo and its associated non-profit, Forever Healthy Foundation, have had a huge impact on the industry in the last few years, and we at LEAF greatly appreciate their contribution to the cause.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
  1. January 14, 2020

    Can it be true that glucosepane is responsible for arterial stiffness and that the body cannot break glucosepane links? The following article reviews studies showing that consumption of omega-3 fatty acids and soy isoflavones reduces arterial stiffness.
    https://www.ncbi.nlm.nih.gov/pubmed/21147858

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