Developing medicines for aging I: Challenges

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Startups developing medicines to slow or prevent the diseases of aging all follow a similar three-step strategy. First they start from data generated by scientists on new ways to extend lifespan and prevent disease–for example, the clearance of senescent cells that was shown to extend mouse lifespans up to 35% and which now underlies Unity Biotechnology’s drug development focus. Then they identify a use in the acute treatment of an age-related disease to get their proposed drug approved by a regulatory agency. Finally, they dream of being able to use it on relatively healthy people before they get sick.

The first two of these steps already represent a significant shift in our approach to drug development. But the last step represents a true departure from how medicine has traditionally been thought of, as something primarily for healing the sick, not for preserving an apparently still healthy body. The best of our current tools for the latter are well-known and often repeated: maintain a healthy diet, exercise, and avoid smoking and other high-risk behaviors. Two to three hours a week of exercise will buy you four years of life, according to cross-sectional studies. This is good news for those of us who are well enough to engage in exercise, but what of those of us who aren’t? Or those of us unlucky enough to contract Alzheimer’s, diabetes or cancer despite it all?

Barriers to approval of new medicines

To really make a dent in aging, new tools–preventative medicines–must be developed, and they must clear two major hurdles. First, they should be incredibly safe. Of the 90% of drugs across all categories that fail clinical trials, a full 30% hit their stumbling block on toxicity tests. Most of these are held to a lower standard than a preventative medication would be, since patients can stomach losing their hair and toenails due to a drug that’s killing their cancer, but not one that’s lowering their risk of eventually contracting cancer. Unnecessary risk to a healthy person’s wellbeing is unacceptable, a point made all the more important to anti-aging therapies’ path to approval by the fact that most will need to be taken on a daily basis for years, magnifying a patient’s exposure to any dangers present in their use.

Secondly, they must prove their effectiveness despite the long response time from beginning a treatment to seeing its outcome. Medicines aimed at preventing diseases like chicken pox or the flu can prove themselves quite quickly, since these diseases develop over a short timescale. But if you give a person who is 50 years old a preventative medication, it will likely be 20 years or more before you can begin measuring whether it had the desired effect. In the meantime, every day the medicine is kept off the market could represent hundreds more people who will contract the disease. However, deploying an ineffective medicine could cost millions or billions in unnecessary medical spending.

Luckily, there is a way to shortcut this lengthy process: biomarkers. These are molecular signals that tip us off as to whether our body is responding appropriately to a medicine before the full effects can be detected. Our next post in this series will go into depth about biomarkers: what they are, how they can be used, and the disagreement surrounding them in the anti-aging community.

James Peyer, PhD

Passionate about aging research since he was 16, James now spends most of his time making investments in biotech companies as a Partner at Apollo Ventures. He was trained as a stem cell biologist at University of Texas Southwestern Medical Center, where he studies the microenvironment of blood stem cells. He co-founded to help provide a portal where people interested in the science of aging could come to learn what was true in the field and help explain to others why he is so excited about aging research.