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Anticorpos monoclonais na dor articular em animais de companhia
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Advisor(s)
Abstract(s)
A artrose é uma doença crónica degenerativa, e a gestão da dor relacionada com esta doença é um
dos grandes desafios clínicos desta década em medicina humana e veterinária. Os anticorpos
monoclonais, amplamente utilizados em investigação, começam a despontar na medicina pelas suas
propriedades inovadoras.
Os anticorpos monoclonais anti-fator de crescimento neuronal (NGF), como o bedinvetmab e o
frunevetmab, são imunoglobulinas obtidas respetivamente pela técnica de "single B cell" em cães e "
PETização" em gatos, técnicas que visam aumentar a especificidade dos anticorpos em relação às
espécies alvos, a fim de limitar a resposta de imunogenicidade induzida.
As propriedades de farmacocinética e farmacodinamia dos anticorpos monoclonais são complexos e
ainda pouco conhecidos, e diferem muito de outras terapias convencionais e de largo espectro
atualmente utilizadas. A utilização dos anticorpos monoclonais anti-NGF no tratamento da dor crónica
associada à artrose em animais de companhia tem mostrado resultados muito promissores, permitindo
associar uma eficácia analgésica a longo prazo (cerca de quatro semanas) após uma única
administração subcutânea, uma especificidade de ação elevada e uma elevada inocuidade relacionada
na sua eliminação.
O objetivo dos anticorpos monoclonais anti-NGF é inibir a ação do NGF, um dos principais fatores
responsáveis pela neuroplasticidade associada à dor osteoarticular crónica. O NGF atua na via da dor
e amplifica os mecanismos de hipersensibilização periférica e central. Os anticorpos monoclonais antiNGF impedem a ligação do NGF ao domínio cinase do recetor da tropomiosina A (TrkA), limitando os
sinais de dor.
Os ensaios clínicos duplos-cegos randomizados realizados em cães e gatos demonstraram uma
eficácia analgésica em vários casos de artrose. Os efeitos adversos severos documentados em
humanos relativos ao desenvolvimento de uma artrose destrutiva aguda e de distúrbios neurológicos
não foram descritos até o momento no cão e no gato, e os vários ensaios clínicos parecem confirmar a
segurança dos anticorpos monoclonais anti-NGF nos animais de companhia.
Osteoarthritis is a chronic degenerative disease, and pain management related to this disease is one of the great clinical challenges of this decade in human and veterinary medicine. Monoclonal antibodies, widely used in research, are beginning to emerge in medicine for their innovative properties. Anti-nerve growth factor (NGF) monoclonal antibodies, such as bedinvetmab and frunevetmab, are immunoglobulins obtained respectively by the "single B cell" technique in dogs and "PETization" in cats, techniques that aim to increase the specificity of antibodies in relation to target species in order to limit the induced immunogenicity response. Pharmacokinetics and pharmacodynamics properties of monoclonal antibodies is complex and remains largely unknown, and differ greatly from other conventional and broad-spectrum therapies currently in use in companion animals. The use of anti-NGF monoclonal antibodies in the treatment of chronic pain associated with arthrosis has shown promising results, allowing the association of long-term analgesic efficacy (about four weeks) after a single subcutaneous administration, high specificity of action and high harmlessness related to its disposal. The objective of the monoclonal antibodies anti-NGF is to inhibit NGF, one of the main factors responsible for the neuroplasticity associated with chronic osteoarticular pain. Nerve growth factor acts on the pain pathway and amplifies peripheral and central hypersensitization mechanisms. Anti-NGF monoclonal antibodies prevent NGF from binding to tropomyosin receptor kinase domain A (TrkA), limiting pain signals. Randomized double-blind clinical trials performed in dogs and cats have demonstrated analgesic efficacy in several cases of osteoarthritis. Severe adverse effects documented in humans relating to the development of rapid destructive arthrosis and neurological disorders have not been described so far in dogs and cats, and the various clinical trials seem to confirm the safety of anti-NGF monoclonal antibodies in companion animals.
Osteoarthritis is a chronic degenerative disease, and pain management related to this disease is one of the great clinical challenges of this decade in human and veterinary medicine. Monoclonal antibodies, widely used in research, are beginning to emerge in medicine for their innovative properties. Anti-nerve growth factor (NGF) monoclonal antibodies, such as bedinvetmab and frunevetmab, are immunoglobulins obtained respectively by the "single B cell" technique in dogs and "PETization" in cats, techniques that aim to increase the specificity of antibodies in relation to target species in order to limit the induced immunogenicity response. Pharmacokinetics and pharmacodynamics properties of monoclonal antibodies is complex and remains largely unknown, and differ greatly from other conventional and broad-spectrum therapies currently in use in companion animals. The use of anti-NGF monoclonal antibodies in the treatment of chronic pain associated with arthrosis has shown promising results, allowing the association of long-term analgesic efficacy (about four weeks) after a single subcutaneous administration, high specificity of action and high harmlessness related to its disposal. The objective of the monoclonal antibodies anti-NGF is to inhibit NGF, one of the main factors responsible for the neuroplasticity associated with chronic osteoarticular pain. Nerve growth factor acts on the pain pathway and amplifies peripheral and central hypersensitization mechanisms. Anti-NGF monoclonal antibodies prevent NGF from binding to tropomyosin receptor kinase domain A (TrkA), limiting pain signals. Randomized double-blind clinical trials performed in dogs and cats have demonstrated analgesic efficacy in several cases of osteoarthritis. Severe adverse effects documented in humans relating to the development of rapid destructive arthrosis and neurological disorders have not been described so far in dogs and cats, and the various clinical trials seem to confirm the safety of anti-NGF monoclonal antibodies in companion animals.
Description
Keywords
Anticorpos monoclonais Anti-NGF Artrose Bedinvetmab Dor Frunevetmab Anti-NGF Bedinvetmab Frunevetmab, Monoclonal antobodies Osteoartritis Pain