The neuromuscular blockade reversal agents, capable of reversing the effect of neuromuscular blocking agents (NMBAs) at the end of anesthesia and therefore restoring muscle function upon resuscitation, represent a medical and economic breakthrough. A team led by Institut Pasteur scientist Pierre Bruhns has worked on the development a new generation of neuromuscular blockade reversal agents.
As well as an anesthetic, some surgeries also require the administration of a neuromuscular blocking agent (NMBA), a drug that induces paralysis, to facilitate intubation and mechanical ventilation. The effects of NMBAs dissipate gradually – when patients wake up, it takes between 30 and 90 minutes, sometimes even longer, for them to recover muscle function. At a time when hospital bed space is limited, this immobilization can clog up intensive care units. Anesthetists are therefore encouraged to administer neuromuscular blockade reversal agents after operations to reverse the effects of NMBAs so that patients are able to move again within a few minutes. This also has the advantage of reducing the duration of intubation and mechanical ventilation and potential adverse effects such as tracheal damage or hospital-acquired infections.
Looking for an alternative to the rocuronium/sugammadex combination
There is currently just one reversal agent for deep neuromuscular blockade (NMB): sugammadex, which only works with two NMBAs, rocuronium and vecuronium. When the joint Institut Pasteur/Inserm team led by Pierre Bruhns began its research in 2019, this drug was too expensive to justify systematic use in France. But with the announcement of patent expiry in early 2026 and entry into the public domain, the price of the sugammadex fell tenfold in 2024 and its use is now widespread. It was therefore no longer financially viable to find an alternative.
But, at a scientific level, the method developed by the team was still valid and the work remains worth pursuing for other potential applications. "The first trials were very encouraging, with paralysis reversed in under two minutes (in an animal model)," says Pierre Bruhns. "So we decided to apply our idea to other NMBAs for which there is currently no reversal agent." There are around 15 such NMBAs. Anesthetists use them if necessary, depending on the case and the patient's allergy history. But given their complex chemical nature, no drugs had previously been found that would reverse their effects.
An antibody-based solution
"Our method bypasses this difficulty," continues the research director. "It involves taking the antibodies produced by patients who have had an allergic reaction to an NMBA, then modifying them to produce neuromuscular blockade reversal agents which do not trigger an allergic reaction when injected into other patients after an operation." As NMBA allergies are rare (1 severe case for every 10,000 anesthetics), the scientists are working with several hospitals – Bichat AP-HP in Paris, as well as three others in Madrid, London and Antwerp – to improve their chances of accessing samples containing antibodies of interest. The new generation of neuromuscular blockade reversal agents they are developing would help reduce pressure on intensive care beds. They would also represent a possible alternative for sugammadex allergy cases, which have risen increasingly since the widespread global use of sugammadex.
Further information: Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in preclinical models, Science Translational Medicine, vol. 16, issue 764, 2024