Comparison of neuromuscular blockade and recovery with botulinum toxins A and F

Intramuscular injection of botulinum toxin A is used to treat focal dystonias. Because immunoresistance has been documented in some patients, other molecular forms of the toxin have been evaluated clinically. The present investigation compared the time course and extent of neuromuscular blockade and recovery of botulinum toxin types A and F using an electromyographic monitoring system implanted in the rat hindlimb. For a given dose, the degree and duration of blockade was more complete with type A toxin. Delayed onset of recovery in animals that received high doses of type A toxin allowed time for denervative changes to prevent a full return to baseline, as confirmed histologically. Conversely, animals receiving type F toxin fully recovered within 30 days at all dose levels. The rapid recovery with type F toxin suggested that neuromuscular transmission was restored via the original terminals rather than through functional collateral sprouting. The reversible nature of blockade with this molecular species puts in question its future clinical utility.