Anagrafe della ricerca

Botulinum toxin (BT) is a potent agent used for the focal treatment of patients with spastic paresis, a neurological condition affecting most children and adults with highly common disorders such as stroke, cerebral palsy, brain trauma, spinal cord injury or multiple sclerosis. After intramuscular injection, BT acts mainly on the presynaptic endings of peripheral cholinergic nerves, cleaving synaptosomal proteins that mediate exocytosis of acetylcholine. Limiting BT diffusion within volumes confining the end-plates minimises the risk of adverse effects resulting from BT migration to sites remote from the injection site, contributing therefore to the success of BT-based therapy. To contend with open issues related to anatomical differences between individuals, formulations of marketed BTs, dose-response curves, and volume and dilution, successful administration of BT requires predicting the diffusion of the toxin effect rather than of the solution containing the toxin in the targeted medium. BREAKing BONDS represents a ground-breaking step beyond the state of the art in this regard, aiming to solve two cardinal issues regarding the optimal delivery of BT to spastic muscles. Building upon recent advances in the detection, processing and modelling of high-density electromyograms, BREAKing BONDS will: i) provide a benchmark for the in vivo assessment of the BT uptake volume in humans; ii) develop a patient-specific model of BT diffusion, ensuring safer and more effective use of BT. Reaching these goals complies with the well-accepted view that BT administration tailored to individuals is likely to promote better short- and long-term effects with a low risk-benefit ratio. In addition to furthering our understanding on the mechanistic basis underpinning BT diffusion and internalisation, the knowledge to be gained from BREAKing BONDS will help decreasing the economic and social burden of spastic paresis, optimising BT delivery and stimulating the emergence of more effective formulations.