Abstract: The present invention provides for methods for diagnosing and treating a motor neuron disease. More specifically, the present invention offers new methods for diagnosing and treating SMA or SMN deficiencies and monitoring treatment. It is possible to identify a subject having a symptom of the disease, and then administer to the subject a therapeutically effective amount of one or more proteins or a gene delivery vehicle or pharmaceutical composition comprising one or more genes selected from the group consisting of Transmembrane protein 41B (Stasimon), Chromosome 19 open reading frame 54 (Rashomon), Tetraspanin 31, Poly (ADP-ribose) polymerase family member 1, Histidyl-tRNA synthetase-like, Chloride channel 7, and Nucleolar protein 1.

Abstract: It has been discovered that pharmacological inhibition of K+ channels (using the FDA-approved broad-spectrum K+ channel antagonist 4-AP) positively benefitted smn mutant phenotypes, a result that is consistent with the defective excitability of motor circuits by their interneuron or sensory neuron inputs being a critical consequence of SMN depletion. Based on these observations, certain embodiments of the invention are directed to methods of treatment of SMA by administering therapeutically effective amounts of one or more potassium channel antagonists, including 4-aminopyridine, 4-(dimethylamino)pyridine, 4-(methylamino)pyridine, and 4-(aminomethyl)pyridine. Other embodiments are directed to new pharmaceutical formulations comprising two or more potassium channel antagonists.