Sirolimus is a relatively new
immunosuppressant drug, and is especially useful in kidney transplants. It was
formerly known as rapamycin as it was found on an Easter Island (called Rapa
Nui in Polynesian) and is an antibiotic of the macrolide class ("-mycin"). It belongs to a class of drugs known as "mTOR inhibitors".
Despite
its similar name, it is not a calcineurin-inhibitor like tacrolimus but has a
similar effect on the immune system as it too prevents production of IL-2 by T
cells, although by a different mechanism. Another effect of the drug is to slow
down proliferation of cells, especially white blood cells including T cells.
The main
advantage of sirolimus over cyclosporine or tacrolimus is that it is not toxic to
kidneys. Transplant patients who take tacrolimus or cyclosporine for a long period of time
tend to develop impaired kidney function or even chronic renal failure, and
this can be prevented by use of sirolimus instead. It is particularly useful in patients with kidney transplants for a condition called
haemolytic uraemic syndrome as this disease is likely to recur in the
transplanted kidney if a cyclosporine or tacrolimus is used.
Sirolimus
can also be used alone or with calcineurin-inhibitors and/or mycophenolate mofetil, to provide immunosuppression without steroids.
The
anti-proliferative effect of sirolimus may reduce the risk of tumour formation
and has also been used in the production of sirolimus-releasing stents used to
treat obstructed coronary arteries.
Other mTOR inhibitors
Everolimus is a new mTOR inhibitor drug
related to sirolimus, and works in the same way. It may have a role in heart
transplantation as it has been shown to reduce long-term scarring of the small
coronary arteries in such transplants. It is not currently licensed for use as
an immunosuppressant in the United Kingdom although it may be used in the
treatment of kidney tumours.
There are
other mTOR inhibitors used for their effect on slowing cell proliferation to
treat tumours or prevent scarring of arteries associated with stent use. These
include ridaforolimus and temsirolimus as anti-cancer drugs and zotarolimus for
arterial stents.
