Phase 3 clinical trials to establish the efficacy of a therapy are in general very expensive, and they are especially very expensive for therapies aimed at extending lifespan. To know the efficacy of such therapies you have to run the trial for many years, before you can learn the lifespans of all of those in the trial.
This may be one reason why pharma firms instead invest in incremental improvements in health tested for those predicted to be near the end of their lives.
Azra Raza claims that the most promising therapies for cancer would be those applied early in the disease. But it is precisely these candidate therapies that would be most expensive to test through a hyper-expensive Phase 3 clinical trial. The result? Unnecessarily slow progress in curing cancer.
(p. B3) Several years ago, scientists studying aging at the Harvard Stem Cell Institute used a somewhat Frankensteinian technique known as parabiosis — surgically joining a young mouse and an old mouse so that they share blood — to see what would happen to the heart and skeletal muscle tissue. They knew from previous research that putting young blood in old mice caused them to grow biologically younger, and that young mice exposed to old blood aged faster.
The Harvard researchers, Amy Wagers and Dr. Richard Lee, found that the old mouse’s heart tissue had been repaired and rejuvenated, becoming young again. In fact, the size of the old mouse’s heart had reduced to that of a young heart.
“We all wondered, what’s the magic stuff in the blood?” said Lee Rubin, a professor of stem cell and regenerative medicine at Harvard and the co-director of the neuroscience program at the Stem Cell Institute. The “magic” they identified was a protein, GDF11, one of tens of thousands produced in the human body. . . . The scientists’ discoveries were published in the journals Cell and Science in 2013 and 2014.
. . .
“We’re interested in proteins like GDF11 that are excreted into the bloodstream because those can cause changes throughout the body,” said Dr. Mark Allen, the chief executive of Elevian. “And those are the kind of changes we want.”
. . .
The initial research into the rejuvenating properties of GDF11 has gotten some pushback from the scientific community. In 2015, after Dr. Wagers and Dr. Lee had published their results, a group of researchers led by David Glass, the executive director of the Novartis Institutes for Biomedical Research in Cambridge, Mass., at the time, challenged the accuracy of their findings in an article in the journal Cell Metabolism. The Harvard researchers subsequently countered the Novartis team’s findings in another 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, who is now at the biotechnology company Regeneron, said in a recent email that he stands by his original work, which showed that GDF11 inhibits, rather than helps, muscle regeneration. But, he added, “our work still leaves open the possibility that there could be positive effects of GDF11 in particular settings.”
Dr. Allen said that since the original controversy, Elevian’s research team has reproduced and extended its original findings in multiple studies, but none have yet been published in peer-reviewed journals. However, institutions unrelated to Elevian have conducted and published many preclinical studies demonstrating the therapeutic efficacy of rGDF11 (the form of GDF11 developed in a lab) in treating age-related diseases.
. . .
A significant challenge lies ahead for all of these companies: Commercializing a drug for aging is nearly impossible because the F.D.A. doesn’t recognize aging as a disease to be treated. And even if it were considered a disease, the clinical studies required to prove that a treatment for it worked would take many years.
“It is likely that clinical studies to see if some drug slows aging — and thereby delays the many consequences of aging — would take a long time,” Dr. Miller said.
. . .
The next big hurdle for Elevian is scaling its manufacturing, which requires specialized equipment and conditions. So much research is being conducted in biotech that contract manufacturers are “full up,” Dr. Allen said. “They are busy with Covid-related work, and there has been a lot of funding in biotech generally,” he added. “So it’s a challenge finding the space that meets our specifications.”
. . .
“By targeting fundamental mechanisms of aging, we have the opportunity to treat or prevent multiple aging-related diseases and extend the health span,” he said. “We want to make 100 the new 50.”
For the full story see:
(Note: the online version of the story has the date July 19, 2022 [sic], and has the title “Can a ‘Magic’ Protein Slow the Aging Process?”)
The published academic articles supporting the promising effects of GDF11 are:
Poggioli, Tommaso, Ana Vujic, Peiguo Yang, Claudio Macias-Trevino, Aysu Uygur, Francesco S. Loffredo, James R. Pancoast, Miook Cho, Jill Goldstein, Rachel M. Tandias, Emilia Gonzalez, Ryan G. Walker, Thomas B. Thompson, Amy J. Wagers, Yick W. Fong, and Richard T. Lee. “Circulating Growth Differentiation Factor 11/8 Levels Decline with Age.” Circulation Research 118, no. 1 (Jan. 2016): 29-37.
The book by Asra Raza that I praise in my introductory comments is:
Raza, Azra. The First Cell: And the Human Costs of Pursuing Cancer to the Last. New York: Basic Books, 2019.