Treatment Use of 3,4-Diaminopyridine

This protocol has provided 3,4 diaminopyridine (DAP) under a treatment-use IND to patients with congenital myasthenic syndrome (CMS). It is currently closed to enrollment.

CMS diagnoses are made based on clinical, electromyographic and molecular genetic findings, and all patients have been referred to the PI for DAP treatment. This study enrolled minors and adults. CMS patients under age 18 years were included if their parent or guardian gave written permission. Minors who turn 18 while in the program will be re-consented as adults. The dose of DAP is determined individually for each patient. Adults are started with a dose of 10 mg 3-4 times daily, increased over several weeks to the dose that produces the maximum symptomatic response, not to exceed 100 mg daily. Pyridostigmine bromide (PB) may be added at low doses and increased to the dose that produced the best response, not to exceed 360 mg daily. In children, equivalent doses of these medications is calculated on a surface area basis. The doses of DAP and PB are periodically adjusted to assure that the smallest effective doses are used. Patients who achieve significant clinical benefit from DAP, as judged by the study PI and the patient, may continue taking DAP as long as the drug is available from the sponsor, and as long as they return for regular follow-up evaluations at the Duke MG Clinic. Patients who are unable to return for regular follow-up will be required to have their local physician obtain DAP for them from the sponsor.

Inclusion Criteria: Diagnosis of congenital myasthenic syndrome (CMS) Women of childbearing potential must have negative pregnancy test and agree to practice adequate contraception while taking DAP Must be competent to give consent Exclusion Criteria: Known seizure disorder Pregnancy Known cardiac arrhythmia or evidence of significant arrhythmia on screening ECG Known hepatic, renal or hematologic disease

Sanders DB, Juel VC, Harati Y, Smith AG, Peltier AC, Marburger T, Lou JS, Pascuzzi RM, Richman DP, Xie T, Demmel V, Jacobus LR, Ales KL, Jacobus DP; Dapper Study Team. 3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia. Muscle Nerve. 2018 Apr;57(4):561-568. doi: 10.1002/mus.26052. Epub 2018 Feb 2.