RESUMO
ABSTRACT The result of more than thirty years of research, anti-CGRP monoclonal antibodies are currently the state of the art for migraine preventive therapy. Their efficacy and safety, supported by an already large and growing body of evidence, are added by many other advantages: an early onset of action, favorable posology, negligible pharmacological interaction, and a broad-reaching efficacy in many challenging clinical contexts. When compared to standard prophylactics, these novel medications seem at least as efficacious, clearly more tolerable and, consequently, with a superior adherence profile. Furthermore, recently published analyses indicate that they are cost-effective, especially among those with chronic migraine. Yet, current guidelines endorse their use only after multiple other preventives have failed or have been deemed not tolerable. Although this recommendation may have been sensible at first, the now available data strongly point that time has come for anti-CGRP monoclonal antibodies to be acknowledged as first-line treatments for migraine patients with severe disability. For these individuals, delaying treatment until several other alternatives have failed incurs in significant losses, both economically and to many relevant aspects of their lives.
RESUMO Frutos de mais de 30 anos de pesquisa, os anticorpos monoclonais anti-CGRP são atualmente o que há de mais moderno no tratamento preventivo da migrânea. À sua eficácia e segurança, já bem estabelecidos por um grande corpo de evidências, acrescentam-se outras vantagens: um início precoce de ação, posologia favorável, mínima interação farmacológica, e eficácia comprovada em uma variedade de contextos clínicos frequentemente desafiadores. Quando comparados a outros profiláticos, estas medicações aparentam ser ao menos tão eficazes, evidentemente mais toleráveis e, portanto, com melhor perfil de adesão. Ademais, estudos recentemente publicados indicam que elas são custo-efetivas, especialmente entre pacientes com migrânea crônica. Ainda assim, as diretrizes atuais orientam o seu uso apenas caso haja refratariedade ou intolerância a múltiplos outros preventivos. Apesar de esta recomendação poder ter sido sensata a priori, os dados disponíveis atualmente corroboram que já é tempo de estes anticorpos monoclonais serem reconhecidos como tratamentos de primeira linha para a migrânea associada à incapacidade grave. Para estes pacientes, demorar a oferecer este tratamento até que outras múltiplas alternativas tenham falhado, leva a perdas significativas, tanto economicamente quanto em múltiplos outros aspectos relevantes das suas vidas.
RESUMO
Stanniocalcin 1 (STC1) and calcitonin gene-related peptide (CGRP) are involved in bone formation/remodeling. Here we investigate the effects of STC1 on functional heterodimer complex CALCRL/RAMP1, expression and activity during osteoblastogenesis. STC1 did not modify CALCRL and ramp1 gene expression during osteoblastogenesis when compared to controls. However, plasma membrane spatial distribution of CALCRL/RAMP1 was modified in 7-day pre-osteoblasts exposed to either CGRP or STC1, and both peptides induced CALCRL and RAMP1 assembly. CGRP, but not STC1 stimulated cAMP accumulation in 7-day osteoblasts and in CALCRL/RAMP1 transfected HEK293 cells. Furthermore, STC1 inhibited forskolin stimulated cAMP accumulation of HEK293 cells, but not in CALCRL/RAMP1 transfected HEK293 cells. However, STC1 inhibited cAMP accumulation in calcitonin receptor (CTR) HEK293 transfected cells stimulated by calcitonin. In conclusion, STC1 signals through inhibitory G-protein modulates CGRP receptor spatial localization during osteoblastogenesis and may function as a regulatory factor interacting with calcitonin peptide members during bone formation.