To determine the efficacy of rapamycin in a xenograft model of inclusion body myositis (IBM). 

Rapamycin is an FDA approved drug used as an immunosuppressant in organ transplant recipients. In a single center pilot study of IBM patients, rapamycin improved secondary endpoints including 6-min walking distance though it did not show efficacy in its primary outcome measure of knee extension strength (Benveniste et al, 2021). Rapamycin may show efficacy via its effect in stimulation of autophagy or via immunosuppression.

Muscle biopsy samples were obtained from 2 patients who were diagnosed with clinico-pathologically defined IBM and 2 people with normal muscle histology for use as control. Xenografts were performed on immunodeficient mice.  After the xenografts had fully matured (3 months), 8 mice with IBM (n = 4) and control (n = 4) xenografts were fed rapamycin and 6 mice with IBM (n = 3) and control (n = 3) xenografts were administered placebo for 3 months. Additional 4 mice with IBM (n = 2) and control (n = 2) xenografts were fed rapamycin and 7 mice with IBM (n = 3) and control (n = 4) xenografts were administered placebo for 6 months. Frozen sections of the xenografts were analyzed by histochemistry and immunohistochemistry in a blinded manner.

Among the IBM xenografts with 3-month treatment, rapamycin treated xenografts showed fewer CD8+ T cells compared with the placebo group. There was no significant difference between the two groups regarding the presence of rimmed vacuoles and abnormal protein aggregates.

In this small pilot study using xenografts, rapamycin reduced the number of endomysial CD8⁺ T cells with 3-month treatment. However, there was no apparent effect on the degenerative features, though the sample size is small. Studies of more IBM xenografts for 6-month treatment are ongoing.