Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal MFN2 mutation. In mice expressing human MFN2 T105M, intermittent mitofusin activation with a small molecule, MiM111, normalized CMT2A neuromuscular dysfunction, reversed pre-treatment axon and skeletal myocyte atrophy, and enhanced axon regrowth by increasing mitochondrial transport within peripheral axons and promoting in vivo mitochondrial localization to neuromuscular junctional synapses. MiM111-treated MFN2 T105M mouse neurons exhibited accelerated primary outgrowth and greater post-axotomy regrowth, linked to enhanced mitochondrial motility. MiM111 is the first pre-clinical candidate for CMT2A.
A 28-year-old nursing student working in Juba, South Sudan, suddenly developed a rash over her mid-right clavicle. Beginning as a 10-cm-diameter erythematous patch with an irregular border, within 24 hours it had developed an increasingly gray, necrotic center, appearing similar to a burn. The patient was seen by 2 local physicians without a diagnosis being made. Ultimately, it was diagnosed as being caused by the toxic hemolymph, pederin, from the Nairobi fly (Paederus). The rash usually affects body parts not covered by clothing; healing time ranges from 7 to 28 days, usually with permanent skin discoloration. Preventive measures include typical antivector precautions, including bed nets, long-sleeve clothing, and avoiding fluorescent lights. If the beetles are found on the skin, brushing them off, rather than crushing them, avoids producing dermatitis. Treatment includes rapidly washing the affected area, applying cold, wet compresses, and possibly treating with antibiotics, steroids, and antihistamines.
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