Can a ‘Magic’ Protein Slow the Aging Process?

this is part of the article Nouveau richeA series about young companies using new science and technology.

Several years ago, scientists studying aging at the Harvard Stem Cell Institute used a somewhat Frankensteinian technique known as parabiosis—surgically combining a young mouse and an older mouse so that they were able to develop blood cells. share – to see what will happen to heart and skeletal muscle tissue. They knew from previous research that ingesting young blood into older mice made them biologically younger, and that young mice exposed to older blood grew faster.

Harvard researchers, Amy Wegers and Dr. Richard Lee, found that old rat heart tissue was repaired and made young again. In fact, the size of an old rat’s heart had grown to the size of a young heart.

“We all wondered, what’s the magic stuff in blood?” Lee Rubin, professor of stem cell 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 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 Wager’s lab found that GDF11 also rejuvenated skeletal muscle tissue. The scientists’ discoveries were published in the journal Cell & Science in 2013 and 2014.

The obvious next question: can GDF11 be used to promote regeneration and repair in humans? In 2017, Dr. Rubin, Wegers and Lee, along with five others, co-founded pharmaceutical start-up Elvion with the aim of commercializing GDF11-based therapies to prevent, slow or reverse aging-related diseases. This is a huge step forward from rats to humans, but it could have dire consequences.

“We are interested in proteins like GDF11 that are excreted into the bloodstream because they can cause changes throughout the body,” said Elvion chief executive Dr. Mark Allen said. “And those are the kind of changes we want.”

Dr. Allen started his first health care company while in medical school at the University of California, Los Angeles, and he left his residency in 2000 to start another. In early 2017, he and his investment partner, Sebastian Gieva, an economist, were looking to start a new approach that would develop therapies targeting the degenerative processes involved in aging. He looked at two dozen potential research projects before deciding on GDF11.

“I had this idea that aging itself might be the target of therapeutic interventions,” Dr. Allen said, “because if we target one aspect of the aging process, we’ll have more options to treat many different diseases.” has the capacity.”

There is preliminary research into the rejuvenating properties of GDF11. Got some pushback from the scientific community. In 2015, after Dr. Wagers and Dr. Lee published their results, their accuracy was challenged by a group of researchers led by David Glass, then executive director of the Novartis Institute for Biomedical Research in Cambridge, Mass. Findings in an article in the journal Cell Metabolism. Harvard researchers later countered the Novartis team’s findings in another paper published later that year in the journal Circulation Research, in which Harvard researchers cited a problem with the Novartis team’s findings.

Dr. Glass, now at the biotechnology company Regeneron, said in a recent email that he is sticking to his original work, which suggests that GDF11 inhibits rather than aids in muscle regeneration. But, he added, “our work still leaves open the possibility that GDF11 may have positive effects in particular settings.”

Dr. Allen said that since the original controversy, Ellivian’s research team has reproduced and expanded their original findings in several studies, but none have yet been published in peer-reviewed journals. However, institutions unrelated to Elevian have conducted and published several preclinical studies demonstrating the therapeutic efficacy of rGDF11 (a laboratory-grown 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.

Alivion is one of several companies rushing to find ways to extend human life span by increasing “health 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 therapeutics” and includes companies such as Altos Labs, which began in January with $3 billion in funding; Calico Life Sciences at Google; Integration Biotechnology; alcachest; and adolescence. About $2 billion in venture capital was invested in pharmaceutical companies focused on anti-aging in 2021, according to Longevity Technology, a market research company and investment platform focused on the longevity sector.

For years, researchers have been looking for drugs that can increase life span and health span. The Intervention Testing Program at the National Institutes of Health began testing drugs — some approved by the Food and Drug Administration, 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 Biology of Aging Research, said anti-aging treatments are often tested on mice because aging in mice is similar to aging in humans. . “Mice and people share most varieties of organs, cell biology and neurons and neurotransmitters, and they often respond to drugs in similar ways,” he said.

All of these companies face a significant challenge: It is nearly impossible to commercialize a drug for aging because the FDA does not recognize aging as a disease to be treated. And even if it is considered a disease, it would take many years for a treatment for it to work, with the clinical studies needed to prove it.

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

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

“We thought, what is the worst disease that has no good treatment and we can treat for the shortest possible duration and show clinical effect?” Dr. Allen said. “We decided that stroke was the right one to target, as it is the No. 1 cause of long-term disability with very limited treatment options.”

Elizabeth Breeze Marsh, medical director of the Comprehensive Stroke Program at Johns Hopkins Bayview Medical Center in Baltimore, said the best treatment for strokes caused by clots (about 87 percent of them) is a type of drug known as tissue plasminogen activator. TPA, or tPA, which must be given within 4.5 hours of the stroke, and surgical removal of large clots.

But according to experts, only 20 percent of stroke victims receive tPA, either because the stroke is not recognized early or because the patient does not qualify because of pre-existing conditions. The researchers at Elivion said that their preclinical (and as yet unpublished) studies have shown that just a few days of treatment with GDF11 can improve recovery after a stroke. They have found that GDF11 reduces inflammation, improves metabolism and stimulates the brain to regenerate blood vessels and neurons.

The next big obstacle for Elivion is scaling up its construction, which requires special equipment and conditions. There is so much research being done in biotech that contract manufacturers are “done,” Dr. Allen said. “They’re busy with COVID-related work, and there’s usually a lot of funding in biotech,” he said. “So finding a location that meets our specifications is a challenge.”

And, like almost all other sectors of the economy, biotech research is facing supply chain issues, which make it hard for Elvion to obtain some of the basic materials needed to conduct research. But the company is growing as fast as we can, and Dr. Allen said he believes the results of its work will have a profound effect on the way we age and how long we live. Will put

“By targeting the fundamental mechanisms of aging, we have the opportunity to treat or prevent many diseases related to aging and to extend health span,” he said. “We want to make 100 the new 50.”