GSE129399
Therapeutic benefit of rapamycin combined with clorgyline or rasagiline in an immunodeficient LAM model
Inhibition of mechanistic target of rapamycin (mTOR) constitutes the standard of care of lymphangioleiomyomatosis (LAM). However, this treatment does not eradicate diseased cells and some patients show progressive decline of lung function. This study provides preclinical evidence for beneficial therapeutic approaches in combination with rapamycin. LAM tumorigenesis is reduced in vivo (ELT3-V3 tumor xenografts) using approved drugs for other human diseases and targeting monoamine oxidase A (MAO-A; clorgyline) or MAO-B (rasagiline). Overall design: Six-week-old female NOD-scid mice were inoculated subcutaneously with ELT3-V3 cells (2×106 cells per injection/site/mouse), and when tumors reached 150-200 mmm3 randomized to control and treatment groups. RNA sequencing of control (n=2; 0.2% carboxymethylcellulose and 0.25% Tween-80), rapamycin (n=2; 0.25 mg/kg/day), rapamycin plus clorgyline (n=2; clorgyline 10 mg/kg/day), and rapamycin plus rasagiline (n=2; rasagiline 1 mg/kg/day). Total of eight tumors analyzed.