What if we take drugs from legitimate diseases and repurpose them for aesthetic anti-aging applications?
This has been an idea that I can’t stop thinking about lately. More thoughts below… (this is still a draft)
Aesthetic medicine has historically been a field filled by murky science. The non-regulated element of supplements/procedures creates a “Wild West” type of environment for aesthetic products [1].
Yet, botox remains the gold-standard therapeutic intervention for cosmetic anti-wrinkle treatment. And there hasn’t been much innovation beyond this and dermal fillers. Why is that? There’s lots of skincare & procedures (i.e. microneedling) to alleviate surface-level symptoms, but there’s a dearth of drugs that precisely target the molecular changes responsible for hair loss/greying, impaired wound healing, wrinkles, etc.
Certain molecular mechanisms behind cosmetic aging phenotypes have been characterized (i.e. we have known molecular targets that could reverse these visible changes when modulated). Even more interestingly, these mechanistic targets already have off-the-shelf drugs previously developed for other diseases.
A hypothesis: There’s lots of low-hanging fruit for off-the-shelf drugs [2] to redirect from disease toward improving appearance. Many of the aesthetic blockbuster drugs today were discovered as accidental side effects while developing the drug to treat another condition [3].
Some interesting examples:
MAPK/ERK inhibitors could reverse hair greying/hair loss and protect against skin aging
MAPK/ERK activation induces hair follicle stem cell aging. This very interesting paper found that miR-31 is the most upregulated microRNA in aged epithelial skin cells. miR-31 downregulates a ciradian clock gene which activates the MAPK/ERK cascade -> hair follicle stem cell aging. MAPK/ERK cascade is also activated during skin photo-aging. Oral and topical administration of FDA approved drug trametinib (MEK inhibitor) protects the mice against hair greying/thinning and skin aging.
Mice given trametinib subjected to radiation-induced skin/hair aging (LIR + T) had thicker, more pigmented fur and had higher rates of wound healing than their counterparts (wound healing gets slower w/ skin aging).
PPAR delta agonists can make you lean + improve muscle endurance (exercise mimic). We always hear people say “I don’t have my 19 yo metabolism anymore”. Theoretically, this drug could help. It burns away fat (especially the bad, visceral fat that accumulates in organs and muscles with age).
PPAR delta is a known regulator of fat burning. Research from Ron Evans lab showed that ppar delta activation in mice drives fat loss and 2x’d their running endurance time (hypothesized mech: it burns away fat deposits in muscle and increases oxidative fibers). While the first ppar delta agonist was shelved due to safety concerns, it is used as an illegal doping agent by athletes. There have been subsequent ppard drugs that have safely been approved for other rare diseases, but curiously, no one has tried to develop it as fat burning pill.
A meta note:
Aesthetic drugs sound rather trivial compared to cancer (which I’ve worked on before). But there’s something that makes me quite excited about it. Biotech gets a bad rep because it costs $1M per drug for a disease you’ve never heard of that affects someone you’ve never met. Ozempic is cool because it made biotech culturally relevant. People care more when it’s something that affects them/something they like. Consumer drugs may end up playing an important role in the realities of bringing aging/preventative medicines to the masses.
[1] People now inject salmon sperm in their skin for anti-aging! The parent company of the manufacturer (Pharma Research Co) has a market cap of ₩3.80 trillion. More on this another time but I think there is a similar unregulated wildness in fertility/reproductive medicine.
[2] Particularly for aesthetic indications, safe/cheap/quick-to-clinic repurposing plays make sense to start.
[3] Viagra, botox, and minoxidil all have serendipitous origin stories as drugs for other disease.
