TRANSLATIONAL NEUROSCIENCES- REVIEW ARTICLE Immunogenicity of botulinum toxins

Abstract Botulinum neurotoxins are formulated biologic pharmaceuticals used therapeutically to treat a wide variety of chronic conditions, with varying governmental approvals by country. Some of these disorders include cervical dysto-nia, post-stroke spasticity, blepharospasm, migraine, and hyperhidrosis. Botulinum neurotoxins also have varying governmental approvals for cosmetic applications. As botu-linum neurotoxin therapy is often continued over many years, some patients may develop detectable antibodies that may or may not affect their biological activity. Although botulinum neurotoxins are considered ‘‘lower risk’ ’ biologics since antibodies that may develop are not likely to cross react with endogenous proteins, it is possible that patients may lose their therapeutic response. Various factors impact the immunoge-nicity of botulinum neurotoxins, including product-related factors such as the manufacturing process, the antigenic protein load, and the presence of accessory proteins, as well as treatment-related factors such as the overall toxin dose, booster injections, and prior vaccination or exposure. Detection of antibodies by laboratory tests does not neces-sarily predict the clinical success or failure of treatment. Overall, botulinum neurotoxin type A products exhibit low clinically detectable levels of antibodies when compared with other approved biologic products. This review provides an overview of all current botulinum neurotoxin products available commercially, with respect to the development of neutralizing antibodies and clinical response