Can a “magic” protein slow down the aging process?

This article is part Upstarta series about young companies using new achievements in the field of science and technology.

A few years ago, scientists studying aging at the Harvard Stem Cell Institute used a somewhat Frankensteinian technique known as parabiosis — surgically fusing a young mouse and an old mouse so they share blood — to see what would happen to the heart and skeletal muscle tissue. They knew from previous research that adding young blood to old mice causes them to become biologically younger, and that young mice exposed to old blood age faster.

Harvard researchers Amy Wagers et al. Richard Lee found that the heart tissue of an old mouse recovered and rejuvenated, becoming young again. In fact, the size of an old mouse’s heart has shrunk to the size of a young heart.

“We all wondered what the magic is in the blood?” said Lee Rubin, a 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 the GDF11 protein, one of tens of thousands produced in the human body. Dr. Rubin’s lab also found that GDF11 in mice stimulated the growth of new blood vessels in the brain and neurons in the hippocampus, a part of the brain associated with learning and memory. Dr. The Wagers lab found that GDF11 also rejuvenates skeletal muscle tissue. The scientists’ discoveries were published in the journals Cell and The science in 2013 as well as 2014.

The obvious next question is: can GDF11 be used to speed up regeneration and recovery in humans? In 2017 Dr. Rubin, Wagers, and Lee co-founded a pharmaceutical startup with five others. Elevian to commercialize GDF11-based therapies to stop, slow or reverse age-related diseases. This is a big step from mice to humans, but it could have serious consequences.

“We are interested in proteins such as GDF11 that are released into the bloodstream because they can cause changes throughout the body,” the doctor said. Mark Allen, CEO of Elevian. “And those are the changes we want.”

Dr. Allen founded his first healthcare company while attending UCLA Medical School and left his residency in 2000 to open a second one. In early 2017, he and his investment partner, economist Sebastian Giva, wanted to start a new company that would develop treatments aimed at the degenerative processes associated with aging. They considered two dozen potential research projects before settling on GDF11.

“I had the idea that aging itself could be the target of a therapeutic intervention,” says the doctor. Allen said, “Because if we target one aspect of the aging process, we have the potential to treat many different diseases.”

Initial research on the anti-aging properties of GDF11 received some rebuff from the scientific community. In 2015, after Dr. Wagers and Dr. Li published their results, a team of researchers led by David Glass, executive director of the Novartis Institute for Biomedical Research in Cambridge, Massachusetts, at the time, questioned the accuracy of their findings. article in the journal Cell Metabolism. Harvard researchers subsequently opposed the Novartis team’s findings. another document published later that year in the journal Circulation Research, in which Harvard researchers mentioned a problem with the Novartis team’s findings.

Dr. Glass, who now works for a biotech company. Regeneronstates in a recent email that he maintains his original workwho showed that GDF11 inhibits rather than aids muscle regeneration. But, he added, “Our work still leaves open the possibility of a positive impact of GDF11 under certain conditions.”

Dr. Allen said that after the initial controversy, the Elevian research group has replicated and expanded on their initial findings in several studies, but none of them have yet been published in peer-reviewed journals. However, non-Elevian institutions have conducted and published many preclinical studies demonstrating the therapeutic efficacy of rGDF11 (laboratory-developed form of GDF11) in the treatment of age-related diseases.

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

Elevian is one of many companies seeking to find ways to increase human life expectancy by extending “life span,” the period of life when a person is generally in good health. This emerging sector of the pharmaceutical industry is often referred to as “longevity therapy” and includes companies such as Altos Labs, which started in January with $3 billion. in financing; Google Calico Life Sciences; Unity Biotechnology; alkahest; as well as youth. Nearly $2 billion of venture capital was invested in anti-aging pharmaceutical companies in 2021, according to Durability Technologymarket research company and investment platform focused on the longevity sector.

For years, researchers have been looking for drugs that can increase lifespan and health. The National Institutes of Health Intervention Testing Program began testing drugs — some FDA-approved, some not — in mice 17 years ago to see if these interventions would extend their lives. Dr. Richard A. Miller, professor of pathology at the University of Michigan and director of the Paul F. Glenn Center for Biological Research on Aging, said anti-aging drugs are often tested in mice because aging in mice is very similar to aging in animals. people. “Mice and humans share organs, cell biology and most varieties of neurons and neurotransmitters, and they often respond to drugs in similar ways,” he said.

All of these companies face a major challenge: commercializing an anti-aging drug is next to impossible because the FDA does not recognize aging as a disease that needs to be treated. And even if it were considered a disease, the clinical studies needed to prove the effectiveness of the treatment would take many years.

“It is likely that clinical studies to find out whether any drug slows down aging — and thereby delays many of the effects of aging — will take a long time,” says the doctor. Miller said.

So, the founders of Elevian determined that the fastest way to bring GDF11 to market was to target a specific disease.

“We thought, what is the worst disease for which there is no good treatment and which we could treat in the shortest possible time and show clinical effects?” Dr. Allen said. “We decided that stroke was the right choice because it No. 1 cause of long-term disability with very limited treatment options.”

Dr. Elizabeth Breeze Marshmedical director of the Comprehensive Stroke Program in Johns Hopkins Bayview Medical Center in Baltimore said that the best treatment for stroke caused by blood clots (about 87 percent of them) is a type of drug known as tissue plasminogen activators, or tPA, that must be administered within 4.5 hours after a stroke and large clots have been surgically removed.

But according to experts, only about 20 percent of stroke victims receive tPA, either because the stroke isn’t recognized quickly enough or because the patient doesn’t qualify due to pre-existing medical conditions. The Elevian researchers said their preclinical (and as yet unpublished) studies have shown that just a few days of treatment with GDF11 can improve stroke recovery. They found that GDF11 reduces inflammation, improves metabolism, and stimulates the brain to regenerate blood vessels and neurons.

The next big hurdle for Elevian is scaling up production, which requires special equipment and conditions. There is so much research going on in biotechnology that contract manufacturers are “packed to capacity,” says Dr. Wilson. Allen said. “They are busy with work related to Covid, and in general, biotech is giving a lot of money,” he added. “Therefore, it is not easy to find a room that meets our requirements.”

And, like almost every other sector of the economy, biotech research faces supply chain issues, making it increasingly difficult for Elevian to obtain some of the basic materials needed to conduct research. But the company is moving forward as fast as it can, and Dr. Allen said he believes the results of his work will have a profound impact on how we age and how long we live.

“By targeting the fundamental mechanisms of aging, we have the ability to treat or prevent multiple diseases associated with aging and extend lifespan,” he said. “We want to make 100 the new 50.”