Biology

Revel Pharmaceuticals Finally Seed Funded to Develop Glucosepane Cross-Link Breakers



I’m pleased to see that the Revel Pharmaceuticals founders have finally sorted out a seed round to fund their work; the establishment of this startup has been in progress for a few years now, and some of us were beginning to think it a lost cause. Revel Pharmaceuticals is the biotech startup established to develop glucosepane cross-link breaker drugs based on work carried out by the Spiegel Lab at Yale. That team, supported by the SENS Research Foundation, first developed a means to synthesize glucospane, and then found bacterial enzymes that can break down glucosepane cross-links.

Glucosepane is the most prevalent form of cross-link observed in aged human tissues, hardy compounds that build up slowly over time as a side-effect of the normal operation of cellular metabolism, and are somewhere between challenging and impossible for even a youthful biochemistry to break down. We humans are just not equipped with the biochemical tools for the job. Cross-linking occurs when structural molecules of the extracellular matrix are linked to one another via bonds with a glucosepane compound, or other only short-lived and thus less harmful molecules, restricting their movement. This is a form of molecular damage that causes loss of elasticity in skin and blood vessel walls, among many other negative effects. The latter is quite serious, the starting point for hypertension, cardiovascular disease, and many other ultimately fatal issues.

The enzymes discovered at the Spiegel Lab and now under development at Revel Pharmaceuticals are a starting point for the development of a therapy that can break down glucosepane cross-links. In my view, breaking persistent cross-links will be as important to achieving rejuvenation in humans as the development of senolytics to destroy senescent cells. A similarly sized industry should arise given one group to light the path, many companies working towards therapies. I hope that the example of one company setting forth on this road to commercial development will soon enough inspire others to follow with their own approaches to the challenge.

Kizoo Technology Capital leads seed round financing at REVEL Pharmaceuticals

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. 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. Revel will 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. 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.”

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