Pediatric Pearls Perfectly Repolished: Part 2 Rapamycin Sheila Fallon Friedlander, MD


In this presentation, Dr Friedlander  discusses the many clinical applications of rapamycin, a target of the P13K pathway which was previously discussed by Dr Frieden.

Is Rapamycin the new wonder drug for kids?

Rapamycin (sirolimus) is an immunosuppressant used to prevent rejection. It is a macrolide and derives from a  Streptomyces species. Rapamycin was first discovered on Easter Island (Rapa Nui) and was originally used an antifungal.. It  blocks the mammalian target of rapamycin (mTOR) pathway by affecting  cyclin-dependent pathways .  These pathways are essentially messengers which can mediate cell  proliferation, metabolism and angiogenesis.

If you think of mTOR as a conductor that is mediating the effect of various growth factors, then  if we have a substance  which can inhibit mTOR, we can impair cell proliferation, cell metabolism and angiogenesis.

Why do dermatologists care about Rapamycin?

There are several diseases with cutaneous manifestions in which  proliferation is a major component of the pathology, for which we have no safe effective treatment. There is evidence that Rapamycin may be effective in treating at least a few of these disorders; in particular  tuberous sclerosis, port wine stains have been investigated,  Rapamycin has also been utilized in an animal model of infantile hemangiomas.

It has been  established that Rapamycin significantly improves facial angiofibroma lesions in patients with TS.  What about port wine stains (PWS)? We know that PWS can recur after PDL treatment. It is hypothesized that the cell trauma of treatment stimulates new blood vessel growth.  Dr Stuart Nelson and others have conducted studies in animal models which show that rapamycin can inhibit regrowth of vessels following laser therapy.


Rapamycin is currently under investigation by Nelson and his colleagues to determine if PWS treatment outcomes can be improved with the use of rapamycin in addition to pulsed dye laser.

One of the challenges with Rapamycin, as found by De Klotz et al, is that of compounding the agent into the right formulation. Scientists are working on optimizing the formulation. Rapamycin is also rather expensive.

Side Effects

Because Rapamycin is an immunosuppressant we have to worry about oral ulcers, diarrhea, and infections, to name just a few concerns. Topical Rapamycin appears to have less side effects.

Rapamycin and Infantile Hemangiomas

In an animal infantile hemangioma model, rapamycin was able to suppress the growth of the tumor via the inhibition of stem cell renewal capability, vasculogenesis, and differentiation.  What’s the difference between angiogenesis and vasculogenesis?  Many healthcare providers are confused regarding angiogenesis and vasculogenesis.  Angiogenesis occurs when new  vessels sprout  and develop  from an existing vessel. Vasculogenesis is de novo new formation of a  vessel presumably from stem cells. The effect of Rapamycin is distinct from that of corticosteroids, i.e., the pathways are  very different.

The Promise of Rapamycin

Rapamycin is a topical  as well as systemic formulation that can inhibit angiogenesis, proliferation and perhaps vasculogenesis. Rapamycin also inhibits stem cell renewal. Given these characteristics, , it could well be an excellent therapy in topical formulation for both angiofibromas and PWS., and perhaps infantile hemangiomas.  However, we  do need to better investigate its possible  side effects before  utilizing on a wide scale basis.