Modern possibilities of drug therapy for patients with botulism

Botulism is not a commonly encountered infectious disease; however, its severity, the potential use of botulinum toxin as a biological weapon, and the lack of truly effective methods and approaches for treating patients with this pathology prevent it from being regarded as a secondary concern. Therapeutic measures for botulism, both currently applied in clinical practice and those under development, can be divided into three complementary but unequal groups in terms of volume, complexity of implementation, and effectiveness. The first group of measures aims to neutralize free botulinum neurotoxin in the patient’s body — whether in the blood, stomach, or intestines — by any available means. The objective is to prevent further toxin entry into nerve cells and, consequently, the progression of clinical signs of specific intoxication. This objective is primarily achieved through the intravenous (for rapid effect) administration of specific antitoxins — in Russia, this role is assigned to botulinum antitoxin serum. The use of immunoglobulins remains limited, and monoclonal antibodies are still under investigation. The second group of measures, predominantly in the development phase with varying degrees of maturity, can be characterized as attempts to create drugs for intraneuronal (antidote) therapy aimed at disrupting the sequential intracellular actions of botulinum neurotoxin — from its internalization into the axonal cytoplasm via the endosomal pathway to the damage of the SNARE protein complex. These include guanidine hydrochloride, 4-aminopyridine (4-AP), 3,4-diaminopyridine (3,4-DAP), tousendanin, and other substances. However, these drugs have not progressed beyond laboratory research and isolated clinical cases with inconclusive results. The third group of therapeutic measures focuses on addressing pathological processes and effects already induced by botulinum neurotoxin at the systemic level. Without underestimating the importance of the continually evolving technology of intravenous infusion therapy for various intoxications, it should be noted that these methods primarily address the consequences rather than the cause. In this regard, some authors consider the possibility of intensive correction of homeostatic disorders through the administration of specialized fluids into the gastrointestinal tract as an addition to or alternative for standard therapy — enteral correction. The use of enteral correction not only detoxifies the gastrointestinal tract but also restores water-electrolyte balance, acid-base homeostasis, hemorheology, microcirculation, pro- and antioxidant balance, intestinal microbiota, and gastrointestinal motility. The elimination of both the intoxication itself and, more importantly, its underlying cause, promotes the activation of reparative processes, including the restoration of neuromuscular transmission through the synthesis of new SNARE proteins.