Can ‘magic’ protein slow down the aging process?

This article is part of Start upseries of articles about young companies harnessing new science and technology.

A few years ago, aging scientists at the Harvard Stem Cell Institute used a somewhat Frankensteinian technique known as parasitosis – surgically grafting a young and an old mouse so that they blood share – to see what happens to the heart and skeletal muscle tissue. From previous research, they know that giving young blood to old mice causes them to grow biologically younger, and that young mice exposed to old blood age faster.

Harvard researchers Amy Wagers and Dr. Richard Lee found that the heart tissue of old mice was repaired and rejuvenated, becoming youthful again. In fact, the size of the old rat’s heart was reduced to that of the young heart.

“We all wondered, what is the magic in the blood?” Lee Rubin, professor of stem cells and regenerative medicine at Harvard and co-director of the neuroscience program at the Stem Cell Institute. The “magic” they identified was a protein, GDF11, one of the Ten thousand produced in the human body. Rubin’s lab also found that GDF11 in mice stimulates the growth of new blood vessels in the brain and neurons in the hippocampus, the part of the brain involved in learning and memory. Dr. Wager’s lab found that GDF11 also rejuvenates skeletal muscle tissue. The scientists’ discovery was published in the journal Cell and Science In two thousand and thirteen and 2014.

The next obvious question: Can GDF11 be used to promote regeneration and repair in humans? In 2017, Dr. Rubin, Wagers and Lee, along with five others, founded a pharmaceutical startup Elevian with the aim of commercializing GDF11-based therapies to prevent, slow down or reverse aging-related diseases. It’s a huge step from a mouse to a human, but could have profound consequences.

“We’re interested in proteins like GDF11 being excreted into the bloodstream because they can cause changes throughout the body,” said Dr Mark Allen, chief executive officer of Elevian. “And those are the kinds of changes we want.”

Dr. Allen started his first healthcare company while attending medical school at the University of California, Los Angeles, and he left his residency in 2000 to start a second. In early 2017, he and his investment partner, Sebastian Giwa, an economist, were looking to start a new company to develop therapies that target the degenerative processes associated with aging. They considered two dozen potential research projects before deciding on GDF11.

“I have this idea that aging itself could be a target for therapeutic intervention, because if we target one aspect of the aging process, then we have potential,” says Dr. Allen. treat many different diseases.”

Early research on the rejuvenating properties of GDF11 has received some feedback from the scientific community. In 2015, after Dr Wager and Dr Lee published their results, a team of researchers led by David Glass, executive director of the Novartis Institute for Biomedical Research in Cambridge, Mass., at the time that point, challenge the accuracy of their findings in an article in the journal Cell Metabolism. The Harvard researchers then countered the Novartis group’s findings in another sheet of paper published later that year in the journal Circulation Research, in which the Harvard researchers cited a problem with the Novartis team’s findings.

Dr. Glass, currently working at a biotech company Regeneronsaid in a recent email that he stands by his original work, suggesting that GDF11 inhibits, rather than helps, muscle regeneration. However, he added, “our work remains open to the possibility that there could be positive effects of GDF11 in specific settings.”

Dr. Allen says that since the initial controversy, Elevian’s team has replicated and extended its original findings in numerous studies, but none have been published in peer-reviewed journals. peer review. However, organizations unrelated to Elevian have conducted and published numerous preclinical studies demonstrating the therapeutic efficacy of rGDF11 (the laboratory-developed form of GDF11) in the treatment of diseases associated with age.

The company is on track to begin human clinical trials in the first quarter of 2023 and has raised $58 million in two funding rounds, with another set to be in mid-2023.

Elevian is one of many companies racing to find ways to increase people’s lifespans by increasing “longevity,” the length of time a person lives in general in good health. This emerging area of ​​the pharmaceutical industry is often referred to as “life-prolonging therapies” and includes companies such as Altos Labs, start in January with 3 billion dollars in funding; Calico Life Sciences at Google; Unity Biotechnology; Alkahest; and Juvenescence. About $2 billion in venture capital has been invested in anti-aging-focused pharmaceutical companies by 2021, according to Technology to prolong lifea market research and investment platform company focused on the longevity sector.

For years, researchers have been searching for drugs that can prolong life and longevity. The Interventional Trials Program at the National Institutes of Health began testing the drugs – some approved by the Food and Drug Administration, some not – in mice 17 years ago to see if the effects could be improved. Will this intervention prolong their lifespan? Dr. Richard A. Miller, professor of pathology at the University of Michigan and director of the Paul F. Glenn Center for Biology for Aging Research, says anti-aging therapies are often tested in mice because they The aging process in mice is very similar to aging in humans. “Mice and humans share organs, cell biology, and most types of neurons and neurotransmitters, and they often respond to drugs in similar ways,” he said.

A significant challenge lies ahead for all of these companies: Commercializing an aging drug is nearly impossible because the FDA does not recognize aging as a disease that requires treatment. And even if it were considered a disease, the clinical studies needed to prove that a treatment for it works would take years.

“It is likely that clinical studies to see if certain drugs slow the aging process – and thus delay many of the consequences of aging – will take time,” said Dr. Miller said.

So the founders of Elevian determined that the fastest way to market GDF11 was to target a specific medical condition.

“We thought, what’s the worst disease that doesn’t have a good treatment and we can treat it in the shortest possible time and show clinical effect?” Dr. Allen said. “We decided that stroke was the right target, because it was The #1 cause of long-term disability with very limited treatment options. “

Dr. Elisabeth Breese MarshMedical director of comprehensive stroke program at Johns Hopkins Bayview Medical Center in Baltimore, states the best treatments for stroke caused by blood clots (about 87 percent of them) is a medicine called tissue plasminogen activator, or tPA, which must be used within 4.5 hours of stroke, and surgical removal of large blood clots.

But according to experts, only about 20% of stroke victims receive tPA, be it because the stroke is not recognized early or because the patient is not qualified due to pre-existing conditions. The Elevian researchers say their preclinical (and unpublished) studies have shown that just a few days of treatment with GDF11 can improve recovery from a stroke. They found that GDF11 reduced inflammation, improved metabolism, and stimulated the brain to regenerate blood vessels and neurons.

The next big hurdle for Elevian is scaling production, which requires specialized equipment and conditions. There is so much research going on in the biotech sector that contract manufacturers have “done the job,” says Dr. “They are busy with work related to Covid, and in general there has been a lot of funding in the biotech sector,” he added. “So it was a challenge to find space that met our specifications.”

And, like most other sectors of the economy, biotech research is facing supply chain problems, which make it difficult for Elevian to obtain some of the basic raw materials needed to make it work. conduct research. But the company is moving as fast as it can, and Dr. Allen said he believes the results of their work will have a profound impact on how we age and how long we live.

“By targeting the underlying mechanisms of aging, we have the opportunity to treat or prevent many diseases related to aging and prolong health,” he said. “We want to turn 100 into the new 50.”

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