Investigation of siRNA as a Treatment for Cushing’s Disease

Cushing's disease results from a pituitary corticotroph adenoma that secretes
adrenocorticotrophic hormone (ACTH). High levels of ACTH stimulate the synthesis of excess
cortisol from the adrenals, the effects of which include hypertension, diabetes, depression,
and weight gain. If left untreated, Cushing's disease carries a 50% five-year mortality rate. At
present, there is no suitable medical therapeutic and transsphenoidal surgery, which is the
first line treatment, has a high rate of recurrence.
RNA-interference is a cellular mechanism that enables gene silencing at the level of mRNA.
It can also be used to reduce gene expression by employing small interfering (si)RNAs that
target the specific gene of interest.
The proopiomelanocortin (POMC) peptide is encoded by the POMC gene and is processed to
release ACTH as well as other hormones.