A drug that could extend women’s fertility by five years – and help them live longer in better health – is safe for a young, healthy population, according to early results of a study.
The research into the repurposing of the immunosuppressant rapamycin has been hailed as a “paradigm shift” in how menopause is studied.
The validating benefits of Rapamycin for Reproductive Aging Treatment (Vibrant) study was designed to measure whether the drug can delay ovarian aging, thereby delaying menopause, prolonging fertility and reducing the risk of age-related diseases.
The study, which will eventually include more than 1,000 women, now has 34 participants aged up to 35, with more women joining every day.
Yousin Suh, a professor of reproductive sciences and professor of genetics and development at Columbia University, and Zev Williams, associate professor of women’s health and chief of the division of reproductive endocrinology and infertility at Columbia University’s Irving Medical Center, led the study led. .
Suh said early results suggest it is realistic to hope the drug can reduce ovarian aging by 20% without women experiencing any of the 44 side effects that rapamycin can have, ranging from mild nausea and headache to high blood pressure and infections.
In fact, Suh said, participants in the randomized, placebo-controlled study had self-reported improvements in their health, memory, energy levels and in the quality of their skin and hair: health improvements consistent with other studies on rapamycin that suggested the medication can increase lifespan by 9-14%, while rejuvenating the immune system and organs that deteriorate with age.
“The results of this study – the first in human history – are very, very exciting. This means that those with age-related fertility problems now have hope where they didn’t before,” Suh said.
“These early results mean that we now have a clear shot at our ultimate goal: the use of rapamycin to extend the life of the ovary and thereby delay menopause, while also extending the life of the woman and improving her health and improve quality of life.”
Suh said the team of at least 12 scientists working on the study, which will cost more than $1 million (£750,000) in total, had “great confidence that the results are just as exciting when we scale up the study”.
“In a way, our results are too good to be true — except because rapamycin is so well studied, we know it’s true,” she said. “These results are like a dream come true.”
This is the first study to look at the core of ovarian aging and try to slow the rate at which it occurs. Previous research on menopause has only addressed it at a symptomatic level.
“Ovarian aging is the fundamental driver of aging in women,” Suh said. “HRT is a patch for aging that has already occurred, but if women take rapamycin in their 30s, when their ovaries are beginning to decline but there are no symptoms yet, they can actually slow down the entire aging process.”
Ovaries constantly release eggs: women lose about 50 each month, with only one reaching ovulation. A small, weekly dose of rapamycin slows down ovaries, so they only release 15 eggs a month. Suh and Williams estimate this reduces the organs’ aging by 20%.
“We know it works with animals – and now we know it’s safe for humans,” said Williams. “Now we just need a larger study to put both parts together.”
Because rapamycin is an inexpensive, generic drug that is already widely used, progress will be rapid once the evidence is established, he said.
“The very characteristics of the drug that make it so promising and give it such great potential to have a rapid and profound impact on women are ironically the very factors that make it difficult to find funders for the study, ” he said.
“That’s why it hasn’t been done before: it’s an expensive study and many women will benefit from it – but there’s no motivation for pharmaceutical companies to invest because there’s no possibility of making money from a -patent remedy not.”
A clinical trial of rapamycin in humans was also considered impossible because it would take decades to detect any longevity effects. However, ovaries age so quickly that change can be measured in six months.
The level of rapamycin used is small: women are given 5 mg a week for three months compared to the 13 mg a day transplant patients may be prescribed for years. But doses are critical: too much rapamycin can stop ovulation altogether, and it is still unknown whether the quality of the follicles will deteriorate over the extra time that ovaries will live, thus producing eggs that are more likely to contain genetic abnormalities.
Another exciting outcome of the study is that all the women continued to menstruate as normal, Williams said. “The implication is that we have reached the perfect dose: if we give too much, menstruation would become irregular or stop.”
Vibrant will report in two years and be followed up by a much larger, “phase 2” study. “Our vision is that women in their 30s and older can make a simple visit to their family doctor if they want more freedom when they have babies,” Suh said.
Women can stop taking rapamycin after menopause, but the greater health benefits the medication appears to offer may make it beneficial for them to continue, she added.
The findings were celebrated by Dr Jennifer Garrisona neuroscientist at the Buck Institute for Research on Aging and the founder of the Global Consortium for Reproductive Longevity and Equality.
“This research is remarkable and marks a paradigm shift in biomedical research for women,” she said. “This is the very first in what should be many studies to confirm the idea that we can prolong ovarian function.
“What we can definitely take from the results so far is that it is now within our reach to keep ovarian endocrine function intact with age.”