Will Success in Reversing Aging Shape the Regulatory System to Accommodate It?

A sizable fraction of the therapies produced by the medical industry are, not to put too fine a point on it, garbage. The benefit is not worth the cost of diverting the resources into the full scale production of the drug, versus those resources going towards some better form of medical research and development. Giving a cancer patient an extra month or two of life, reducing fibrosis in the liver by 10% over a year of treatment, incrementally improving mitophagy to half the degree that exercise achieves, and so forth. Small molecule development in particular excels at producing this sort out outcome, as the effects on gene expression and protein interactions produced by small molecules tend to be much smaller than the effects produced by genetic interventions carried out during proof of concept studies in the lab.

The overbearing, overburdened regulatory system for medical development has become optimized towards determining the difference between a garbage therapy that produces a small positive effect and a garbage therapy that has no positive effect. That goal is an expensive proposition in principle, even setting aside all of the unnecessary costs imposed by regulators. When that regulatory system starts from the position of "first, do no harm," one can see how it may evolve to use the lever of imposed cost to discourage an influx of treatments that are not really expected to meet a sane cost-benefit threshold. Many of us feel that it isn't the role of government employees to be making that decision for everyone, but that is the situation, alas.

Given evident, clear success in medical development, however, the system becomes far less of a roadblock. When a new therapy definitively cures a rare disease, as happens ever more often in this era of progress in biotechnology, the sponsoring team might find regulators moving directly from a phase II trial in 20 or so patients right into clinical approval. The usual obstacles and further costs put in place for marginal therapies melt away in this situation. Severe diseases tend to be accompanied by clear success criteria in the form of disease symptoms and patient mortality. It is obvious that a therapy has produced a cure, or managed the condition down to negligible pathology.

Will this also be the case for the first therapies to produce meaningful rejuvenation? The immediate issue here is that there is no practical, consensus measure of rejuvenation. Yes, epigenetic clocks exist alongside clocks derived from other omics data, but we are nowhere near the point at which the world, or regulators, would accept a reliable ten year reversal of epigenetic age in patients at face value, as representing actual rejuvenation. But the real question is whether a proven rejuvenation therapy would in fact produce a melting away of regulatory obstacles, given that yet to be established consensus measure of age-related decline.

People will think very differently about a cure for multiple sclerosis versus a rejuvenation therapy that grants ten additional healthy years, on balance. Multiple sclerosis exhibits what regulators call "high unmet need," a condition that disables and kills, and for which current treatments do too little. A robust cure for multiple sclerosis would rapidly reverse disabling symptoms in an obvious way. In comparison, a therapy that gives people ten additional years, and turns back the clock in terms of measures of aging, has (a) less evident immediate benefit, and (b) will be used by far more people if approved by regulators. That changes the calculus in the minds of regulators.

It is interesting to contemplate future obstacles, or lack of same, but the first step remains the production of working rejuvenation therapies. The most important of those presently heading towards significant, widespread clinical use in the 2030s are senolytics and perhaps the first uses of partial reprogramming. It will remain to be seen as to how great an improvement they produce in late life human health, and how much of a roadblock is put in their way by regulatory bodies.