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What’s a biomarker?
A biomarker (short for “biological marker”) is a measurable indicator of the medical state of a person or animal. They can be used to diagnose diseases, identify health-risks, and monitor specific changes in the body.
White blood cells are a biomarker for infections:
They’re measurable. White blood cell count is measured from a blood sample.
They’re an indicator. If you have more white blood cells than usual, it indicates the existence of an infection.
Most biomarkers are quite complex. Biomarkers are indicators of certain conditions in the body. This may be part of the cause, the result, or side effect of the condition. White blood cells are a direct result of infection. Other biomarkers – like insulin-growth factor 1 (IGF-1) which is associated with aging – have relationships that are more difficult to untangle. We don’t yet know whether a decline in IGF-1 causes aging, or aging causes a decline in IGF-1, or something else entirely causes them both.
Ahhh, biology. I wish it were simple.
Biomarkers in aging
Some chemicals in our body increase or decrease as we age. For example, klotho is a protein that exists in the bloodstream. As humans and mice age, levels of klotho in the body decline. This decline is associated with physical changes such as cognitive decline. In other words, klotho is an aging biomarker.
Interestingly, manipulating klotho levels also modulates aging. In humans, a reduction in klotho has been associated with kidney failure. In mice, an overexpression of klotho has been associated with a longer lifespan. klotho may be more than a biomarker that tracks changes– it might be the driver of change.
So why do we need biomarkers? They can be used as endpoints.
Definition detour
Clinical endpoints characterize how a patient “feels, functions, or survives”, after receiving a treatment. Unlike biomarkers, clinical endpoints are more subjective.
Take a cancer patient after their treatment, for example. Do they feel healthier? Did they survive? These clinical endpoints help determine whether the treatment they received was effective.
The problem with clinical endpoints is that they’re only available post-treatment. When treating a cancer patient, it’s better to know sooner rather than later if the treatment isn’t working. This is where biomarkers come in handy.
Surrogate endpoints are biomarkers that can be used as a stand-in for clinical endpoints. For a biomarker to be a surrogate endpoint, “there must be solid scientific evidence that a biomarker consistently and accurately predicts a clinical outcome, either a benefit or harm.”
Why biomarkers are useful
For physicians
Surrogate endpoints can act as signposts that a treatment is working (or not) and allow them to change course if necessary. Clinical endpoints, on the other hand, may arrive far too late to ensure the patient’s health and safety.
For biotech and pharma companies
Surrogate endpoints help speed up the development of drugs by allowing for shorter, partial, or parallel studies to take place.
Let’s take klotho as an example. If an increase in klotho is proven to be associated with an increase in lifespan, klotho can be used as a surrogate endpoint. And, if a drug is shown in clinical trials to increase klotho in the bloodstream, then it may be reasonable to assume that the drug is effective in extending lifespan.
On the other hand, using a clinical endpoint – “did they live longer than usual?” – to determine whether a drug extends lifespan would take a lifetime. Literally. (And then some, if the drug worked.)