Botulinum toxin therapy, immunologic resistance, and problems with available materials

Botulinum toxin injections have become an extremely useful therapeutic modality in the treatment of certain segmental movement disorders such as blepharospasm, adult onset spasmodic torticollis, spasmodic dysphonia, and oral mandibular dystonia. Clinical efficacy is substantially better, and complications of this therapy are significantly lower than alternative approaches for many of these disorders. Short-term complications have often been the result of undesirable diffusion away from the injection location, resulting in transient weakness. The study reported by Jankovic et al ^[1] deals with immunologic resistance, the major long-term complication of repeated injections.

Historic concern becomes a current reality.

Botulinum toxins have long been known to be antigenic proteins, with different serotypes characterized by the use of neutralizing antibodies. Because botulinum toxin is used to treat chronic diseases and repeated injections are necessary over a long period of time, sensitization after repeated injections is an ongoing concern of both clinicians and regulators from initial studies to the present.

Concern regarding antibody production was present in the original formulation for clinical studies. Initial emphasis was placed on the drying to achieve preservation to prevent contamination. However, the original method of drying had serious problems because of 80 to 90% loss of activity of the material in this process. In 1979, Schantz ^[2] and Scott were perfectly aware that the inactivated botulinum toxin may be as antigenic as active toxin; however, there was insufficient clinical experience to assess the significance of this observation. This formulation approved in the United States has become accepted over the past decade. By altering the drying process, it is now possible to prevent botulinum toxin inactivation, hence lowering incidental toxoid accumulation within the vials. ^[3]

Alternative immunotypes: the issue of bioequivalency and efficacy.

Once neutralizing antibodies are present to immunotype A, the clinical results of subsequent injections are obliterated. ^[4-7] Although other immunotypes of botulinum toxin are under development, clinical studies indicated that distinct …