To test motor fiber excitability in early affected patients with transthyretin (TTR)-type familial amyloid polyneuropathy (TTR-FAP) before and during tafamidis treatment.

We examined the left median nerve of 21 healthy-matched controls and 10 early affected TTR-FAP patients using the automated threshold-tracking program, QTRAC. TTR-FAP patients were tested one day before the initiation of tafamidis treatment, 3 and 6 months later.

The drug was well-tolerated in all patients; there was no drop-out. No statistical difference was found between healthy controls and TTR-FAP patients at study entry. On treatment, both stimulus intensity for 50% of the maximal motor response and rheobase increased significantly from entry to the last evaluation at 6 months (P<0.05). Strength duration time constant decreased significantly from the 3rd to the 6th month of evaluation (P<0.05). There was also a “fanning-out” effect on the late depolarization phase (TEd 90–100ms) as well as a shortened relative refractory period from study entry to the 6th month of evaluation.

Threshold-tracking of median nerve motor fibers is not a helpful technique for the early diagnosis of TTR-FAP patients. Tafamidis was well-tolerated. We observed possible membrane hyperpolarization during treatment. Threshold tracking can contribute to documenting the action of new drugs to treat neuropathies. Tafamidis may change nerve electrical properties by reducing the burden of amyloid fibrils.