Oral administration of creatine monohydrate retards progression of motor neuron disease in the wobbler mouse.
OBJECTIVE
Creatine has a neuroprotective effect in mutant superoxide dismutase (G93A) transgenic mice, an animal model of motor neuron disease (MND). Treatment with creatine monohydrate enhances muscle strength in patients with neuromuscular disorders. The purpose of our study was to determine whether administration of creatine monohydrate can attenuate progressive disease in wobbler mice.


METHODS
After an initial diagnosis of disease at the age of 3-4 weeks, creatine monohydrate (5 or 50 mg/kg, po) or vehicle was given to wobbler mice daily for 4 weeks in a blinded fashion. We compared symptomatic and neuropathological assessments among the three groups.


RESULTS
Creatine levels in biceps muscles were increased by approximately 20% following administration of higher-dose creatine monohydrate. In comparison with vehicle, treatment with higher doses of creatine monohydrate potentiated grip strength, attenuated forelimb contracture and increased the weight of biceps muscles. Mice treated with higher doses of creatine monohydrate showed retarded denervation muscle atrophy in the biceps muscles and reduced degeneration of the spinal motor neurons. Thus, oral administration of creatine monohydrate delayed the progression of disease in wobbler mice.


CONCLUSIONS
Our results indicate that this molecule may have therapeutic potential in human motor neuropathy or MND.
Ikeda
K
K
Fourth Department of Internal Medicine, Toho University, Ohashi Hospital, Tokyo, Japan.
Iwasaki
Y
Y
Kinoshita
M
M
D000284:Administration, Oral; D000818:Animals; D002452:Cell Count; D003401:Creatine / Q000008:administration & dosage* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005552:Forelimb / Q000473:pathology; D018737:Hand Strength; D051379:Mice; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000188:drug therapy* / Q000473:pathology; D009046:Motor Neurons / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D013116:Spinal Cord / Q000473:pathology
D003401:Creatine