Targeting protein homeostasis in sporadic inclusion body myositis.
Sci Transl Med
; 8(331): 331ra41, 2016 Mar 23.
Article
en En
| MEDLINE
| ID: mdl-27009270
ABSTRACT
Sporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients more than 50 years of age. Previous therapeutic trials have targeted the inflammatory features of sIBM but all have failed. Because protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature of the disease. Using rat myoblast cultures, we found that up-regulation of the heat shock response with arimoclomol reduced key pathological markers of sIBM in vitro. Furthermore, in mutant valosin-containing protein (VCP) mice, which develop an inclusion body myopathy, treatment with arimoclomol ameliorated disease pathology and improved muscle function. We therefore evaluated arimoclomol in an investigator-led, randomized, double-blind, placebo-controlled, proof-of-concept trial in sIBM patients and showed that arimoclomol was safe and well tolerated. Although arimoclomol improved some IBM-like pathology in the mutant VCP mouse, we did not see statistically significant evidence of efficacy in the proof-of-concept patient trial.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas
/
Miositis por Cuerpos de Inclusión
/
Homeostasis
Tipo de estudio:
Clinical_trials
Límite:
Animals
/
Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article