Charcot-Marie-Tooth disease (CMT) is a slowly progressing hereditary neuropathy with a diverse clinical presentation. The most classic phenotype includes distal lower extremity weakness with gait impairment progressing to upper extremity weakness combined with gradual loss of upper/lower extremity sensation. No pharmacological therapy has proven effective with management usually focusing on supportive care including physical rehabilitation, orthotics, and avoidance of neuropathy-exacerbating factors.

We present four case reports of CMT patients who experienced improvement in their neuropathy-related symptoms following treatment with Droxidopa.

The initial therapeutic effect was observed in a 55-year-old male patient given Droxidopa for concomitant Neurogenic Orthostatic Hypotension. Once on the medication, the patient reported noticeable improvement in gait/leg weakness evidenced by regaining his ability to play golf. His physical therapist documented objective improvement in functional testing following Droxidopa initiation. When insurance forced a switch to Fludrocortisone and Midodrine, he experienced a relapse in weakness consisting of inability to play golf and difficulty standing. Symptom improvement was restored once Droxidopa was restarted. This patient has maintained symptomatic relief for over nine years despite progression of CMT symptoms. In another case, a musician with hand weakness due to CMT was able to play the guitar again while on Droxidopa. A third patient reported increased strength 30-60 minutes after taking Droxidopa and a return of weakness after 4-6 hours if a dose was missed. In the fourth case, the patient experienced four years of consistent improvement in weakness and balance with Droxidopa followed by rapid decline when Droxidopa was discontinued.

Droxidopa may offer symptomatic relief for patients with CMT, especially motor symptoms. While further studies with larger patient populations and objective measures of improvement are needed to establish a definitive link, the observed improvements in functional motor daily activities, patient satisfaction and fine motor function suggest a potential therapeutic benefit.