AUTHOR=Ceccanti Marco , Libonati Laura , Ruffolo Gabriele , Cifelli Pierangelo , Moret Federica , Frasca Vittorio , Palma Eleonora , Inghilleri Maurizio , Cambieri Chiara 

TITLE=Effects of 3,4-diaminopyridine on myasthenia gravis: Preliminary results of an open-label study

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.982434

DOI=10.3389/fphar.2022.982434

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 3,4-diaminopyridine (3,4-DAP) can lead to clinical and electrophysiological improvement in myasthenic syndrome; it may thus represent a valuable therapeutic option for patients intolerant to pyridostigmine.</p><p><bold>Objective:</bold> to assess 3,4-diaminopyridine (3,4-DAP) effects and tolerability in patients with anti-AChR myasthenia gravis.</p><p><bold>Method:</bold> Effects were monitored electrophysiologically by repetitive nerve stimulation (RNS) and by standardized clinical testing (QMG score) before and after a single dose administration of 3,4-DAP 10 mg per os in 15 patients. Patients were divided according to their Myasthenia Gravis Foundation of America (MGFA) class into mild and severe.</p><p><bold>Results:</bold> No significant side effects were found, apart from transient paresthesia. 3,4-DAP had a significant effect on the QMG score (<italic>p</italic> = 0.0251), on repetitive nerve stimulation (<italic>p</italic> = 0.0251), and on the forced vital capacity (<italic>p</italic> = 0.03), thus indicating that it may reduce the level of disability and the decremental muscle response. When the patients were divided according to the MGFA classification, 3,4-DAP showed a positive effect in the <italic>severe</italic> group, either for the QMG score (<italic>p</italic> = 0.031) or for the RNS decrement (<italic>p</italic> = 0.031). No significant difference was observed in any of the outcome measures within the <italic>mild</italic> group (<italic>p</italic> &gt; 0.05). A direct effect of 3,4-DAP on nicotinic ACh receptors (nAChRs) was excluded since human nAChRs reconstituted in an expression system, which were not affected by 3,4-DAP application.</p><p><bold>Conclusion:</bold> Our results suggest that 3,4-DAP may be a useful add-on therapy, especially in most severe patients or when immunosuppressive treatment has not yet reached its full effect or when significant side-effects are associated with anticholinesterase.</p>