A drug named after Easter Island started life as a failed antifungal
In 1972 scientists isolated a compound from soil bacteria collected on Easter Island and named it rapamycin, after Rapa Nui. It was meant to fight fungi. Instead it turned out to calm the immune system and halt cell growth, and it now protects transplanted kidneys and coats heart stents.
The molecule, known medically as sirolimus and sold as Rapamune among other brands, is made by the bacterium Streptomyces hygroscopicus. Its antifungal career ended once researchers found it strongly suppressed immune responses and cell proliferation. The reason is a protein it blocks, which scientists named mTOR, short for mammalian target of rapamycin. Inhibiting it makes T cells and B cells less responsive to the signalling molecule interleukin-2. American regulators approved the drug in 1999.
Transplant medicine is its main arena, especially kidneys. Its big selling point over the older calcineurin inhibitor drugs is that it is far gentler on the kidneys, which long-term calcineurin treatment can damage. It can also form part of regimens that avoid steroids. The trade-offs include slower wound healing and low platelet counts, so some centres wait weeks or months after surgery before starting it, and regulators have warned of infection risk and, since 2008, of possible declines in kidney function. Blocking a related protein complex can cause diabetes-like effects such as insulin resistance.
Other uses followed its growth-stopping power. Coated onto coronary stents, it releases slowly and cuts the rate at which arteries narrow again after angioplasty, though such stents may raise clot risk. In May 2015 it became the first approved drug for lymphangioleiomyomatosis, a rare progressive lung disease mainly affecting women of childbearing age, in which mutations in a gene called TSC2 switch on the mTOR pathway. A trial compared it with placebo in 89 patients over 12 months.
Skin and blood vessels benefit too. Facial angiofibromas affect 80 percent of people with tuberous sclerosis complex; a review of 16 studies covering 84 patients found topical sirolimus improved 94 percent of them. The FDA approved it for angiofibromas in April 2022, and a gel version was authorised in the European Union in May 2023. It is also increasingly used for vascular malformations and tumours.
Source: Sirolimus
