Can restoring elastin with existing drugs improve longevity?

Elastin Biosciences moves into lifespan studies following positive preclinical results in mice.

Back in September, we brought you the news that Elastin Biosciences had emerged from stealth, boasting novel drug combinations that demonstrated aortic elasticity improvements in mice. The company, which is the first to emerge from longevity company builder Longaevus Technologies, is now moving into studies to determine if the drug combinations impact lifespan in mice.

Longevity.Technology: Co-founded by renowned longevity researcher Dr Alexey Moskalev, Longaevus is built on the premise that successfully addressing five key aspects of aging will enable the introduction of “desperately needed aging interventions to the world in a timely manner.” In addition to Elastin Biosciences, which is working on solutions to improve tissue integrity and flexibility, Longaevus is also targeting four other hallmarks of aging, including: repair of physiological barriers, addressing genome instability, reversal of mitochondrial dysfunction, and restoration of autophagy regulation.

To learn more about how targeting the protein known as elastin fits in to this wider vision, we caught up with the CEO of Elastin Biosciences, Sherif Idriss.

The primary function of the elastin protein is to provide elasticity and resilience to connective tissues, including our skin, blood vessels and lungs. However, the elastin in our bodies degrades as we age, contributing to visible signs of aging as well as decreased vascular flexibility, which is linked to a wide range of age-related health conditions, including cardiovascular disease, the leading global cause of death. Elastin Biosciences is on a mission to reverse that degradation at a systemic level.

A classical drug discovery approach

A neuroscientist turned entrepreneur, Idriss has been involved in Elastin Biosciences since its inception – initially as a consultant and now as its CEO. The first steps towards the formation of the company began in what Idriss describes as a “classical approach” to drug discovery, looking for opportunities to reverse elastin degradation in the arteries.

Can restoring elastin with existing drugs improve longevity?
Sherif Idriss is CEO of Elastin Biosciences.

“We did it the old way, looking at the literature to identify potential combinations of existing compounds – including drugs already approved for other indications and those still in the research phase,” he says. “While elastin has been studied a lot in terms of skin, no one had yet looked at how these compounds affect elastin in the aorta or at systemic level in vivo. So, we came up with several combinations of anti-inflammatories to reduce elastin degradation, and drugs that activate a pathway that eventually leads to elastin deposition.”

Idriss led the company’s preclinical experiments, conducted at the University of Oxford, which sought to identify novel drug combinations that inhibit elastin degradation and foster its deposition in the arteries of aged mice.

“We looked at old mice that had elastin degradation,” he says. “Similar to humans, it’s normal that elastin degrades with age in mice – their arteries become stiff, and they get atherosclerosis or clotting or other forms of long-term inflammation in the artery. So, an aged-mouse model is quite relevant for this work.”

Increased elastin expression and aortic elasticity

While Idriss and his team felt there was a good chance that the drug combinations would yield positive results, they were taken aback by how well the mice responded.

“We never thought it would go as well as it did,” says Idriss. “We were concerned about potential side effects, but apart from itching, which is normal when you’re injecting, there was nothing else – the mice were happy, healthy, and only received the drugs twice a week, which was not stressful for them.”

The experiments, which looked at the effects of four different potential drug combinations, ended after 12 weeks and produced some pleasantly surprising findings.

“Of the four different formulations, three showed fantastic results, increasing elastin expression fivefold, which is crazy,” says Idriss. “The preliminary data also shows that the quality of the elastin fibers is actually very good as well. It’s not just that they’re increasing, they’re increasing and forming decent fibers in such old mice, which was a very big deal for us.”

The researchers also looked at the actual functionality of the arteries.

“We also found that the aortas of the treated mice were more elastic and also stronger than those of the untreated mice,” says Idriss. “We now need to compare the data with younger mice. But based on the literature, we believe the improvements we’ve seen are comparable to a mouse aged a few months younger.”

Next steps include lifespan studies

Elastin Biosciences is now conducting additional analysis on the mouse data, including looking at the effects on the brains of the mice, as well as inflammatory markers and NAD levels in the blood, and further analysis of the quality of elastin produced. 

In keeping with its parent company’s longevity mission, another major preclinical step for Elastin Biosciences is to start exploring the potential impact of the three formulations on lifespan.

“We are immediately starting a lifespan study in mice on these drug combinations,” says Idriss. “We also want to demonstrate that we have anti-inflammatory effects, that we have health effects on the brain, and that we have positive effects on other organs as well, including the liver.”

Idriss reveals that the first therapeutic indications for the company will likely include abdominal aortic aneurysm, a swelling in the aorta, and Marfan syndrome, a disorder of the body’s connective tissues.

“Because the proof of concept has been exceptionally good, we are already looking into IND-enabling studies,” he says. “We’re no longer asking if the drug combinations work, we’re just getting everything in order in the right way from a regulatory point of view to take them to market.”

According to Idriss, the company is currently funded through the next two years, which should enable completion of all preclinical work on the two initial indications, as well as confirming any longevity related effects in mice.  

Photograph: Elastin/IT Tech Science/Shutterstock