WHY THIS MATTERS IN BRIEF
A bacterium found on Easter Island is the source of a drug that extends life in lab animals, and researchers want to know if it could do the same for humans, but research and regulatory hurdles may make the road ahead a long one.
What if you could become younger just by taking a pill? And would you just take one, or would you keep going? These are the questions you might soon find yourself asking.
Hot on the heels of the world’s first human anti-aging trial, which, ironically, itself was announced just a few weeks ago a second healthcare company, PureTech, who are licensing two new drug molecules, and the right to use them to combat aging and age related disease, from Novartis, have announced that they’re going to be trialling their own anti-aging pill on humans later this year under the umbrella of a new joint venture with Novartis called resTORbio.
The aim of the first trial will be to test whether or not the drugs rejuvenate aged human immune cells – after all, you have to start somewhere.
The new drug is a derivative of Rapamycin, a compound first discovered oozing from a bacterium native to Easter Island Rapa Nui. Thanks to its broad effects on the immune system Rapamycin is already used in transplant medicine as an immune suppressant, and a version is sold by Novartis as the anticancer prescription Afinitor.
What’s even more interesting about Rapamycin though is its reputation as the most consistent way to postpone death – at least in laboratory species – and it lengthens the lives of flies, worms, and rodents as well. For example, feed the compound to mice – mice get all the good drugs – and on average they live 25 percent longer.
“It doesn’t make them immortal, but it’s pretty good,” says David Harrison of the Jackson Laboratory, who participates in the Intervention Testing Program, an effort of the National Institute on Aging in which drugs with longevity promise are independently tested in mice over a period of years.
“It’s the most exciting intervention that we have,” he said, “it also works at any age, and that makes it interesting.”
While there is a current study underway in Seattle to see if Rapamycin extends the lifespan of dogs, see the video below, so far there haven’t been any formal studies on whether or not it can lengthen people’s life spans.
There have been many reasons companies haven’t been keen to pursue potential anti-aging treatments. Scientifically, longevity pills remain an out there idea, the domain of cranks and quacks, and clinically it’s difficult to prove a drug extends life as it would take too long. Then, regulations wise, there’s no clear path forward, as aging hasn’t generally been recognised as a disease you can treat – although here too there are an increasing number of people who advocate it’s a disease that, like any other disease, can be cured if we simply know how.
It’s tough trying to create an anti-aging pill but recently venture capitalists, including Google, who used to run from such ideas have begun investing billions of dollars in the field.
Brian Kennedy, who researches aging at the Buck Institute, says the Novartis drug is “groundbreaking” because of its impact on the effects of age.
“No one has the stomach to do longevity studies,” he said in an interview last year, “or you can do what Novartis did, which is to choose a property of aging and see if you can slow it down.”
Novartis says it will soon be reporting more results from its studies in the elderly but the company also said that it had decided that that specific area of research no longer fitted with its priorities.
“We will stop developing [Rapamycin] for age related disorders,” says Jeffrey Lockwood, a Novartis spokesperson, “it’s outside of our current strategy.”
Instead, Novartis decided to sell the program to PureTech, who are investing $15 million in the new program, in exchange for an ownership stake in the new company resTORbio. The startup’s CEO, Chen Schor, wouldn’t say exactly what direction it planned to take, other than that the company would build on Novartis’s data.
“We are talking a very pragmatic approach and will prioritize indications where we hope the data could get us approval using these compounds if you can change the decline in function of the immune system,” says Schor.
In the short term the startup will try to use the Novartis drugs to reverse what it calls “immunosenescence,” or detrimental changes to the immune system that occur with age and over time it will increase the scope of the project. In part, that might include trying to restore certain types of T cells, which become exhausted and don’t remain vigilant against cancer and infections.
“They get old and grumpy but hang around and secrete pro-inflammatory cytokines, and that have health and aging consequences,” says Joseph Bolen, chief scientific officer of PureTech.
Rapamycin acts on what is called the mTOR complex, a set of genes that play a basic role in regulating the metabolism of cells. When mTOR is blocked, it can push cells into a life-extending survival mode.
“This happens to be one mechanism that is actionable with a drug and not, say, calorie restriction,” says Bolen, “I think this is a practical way to go about the modulation. What the biology tells you is that what was observed in many other species looks as though it is going to hold in humans.”