Table 3.

Studies of mTOR inhibitors in multiple sclerosis patients.

Type of Study	Patients Included	Main Results	Ref.
Double-blind, placebo-controlled phase II trial	N = 296 patients with active, relapsing MS relapses; 2, 4, 8 mg temsirolimus/d or placebo for 9 months	8 mg group: ~50% reduction in active lesions and relapses, mouth ulcers, menstrual abnormalities	[107,108]
Non-randomized, prospective, controlled	N = 50 RRMS with metabolic syndrome; N = 20 metformin, N = 20 untreated	Metformin group:↓ new/expanding T2 lesions, ↓ Gd+ lesions, ↓ myelin-specific T cells, ↑ Tregs	[110]
Non-randomized, prospective, controlled	N = six RRMS patients on 2 mg rapamycin/d for 6 months N = six healthy controls	↓ IFNγ, ↑ TGFβ in serum of patients after 6 months	[105]
Non-randomized, prospective, uncontrolled	N = eight RRMS patients on 2 mg rapamycin/d for 6 months	↑ Tregs, ↓ in mean lesional area size after treatment	[106]

Abbreviations: ↓/↑: decrease/increase level; Gd+: gadolinium-enhancing lesions; d: day; IFNγ: interferon gamma; MS: multiple sclerosis; mTOR: mammalian target of rapamycin; RRMS: relapsing–remitting MS; TGFβ: transforming growth factor beta; Tregs: T regulatory cells.