Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition.
Early treatment with the histone deacetylase inhibitor, trichostatin A, plus nutritional support extended median survival of spinal muscular atrophy mice by 170%. Treated mice continued to gain weight, maintained stable motor function, and retained intact neuromuscular junctions long after trichostatin A was discontinued. In many cases, ultimate decline of mice appeared to result from vascular necrosis, raising the possibility that vascular dysfunction is part of the clinical spectrum of severe spinal muscular atrophy. Early spinal muscular atrophy disease detection and treatment initiation combined with aggressive ancillary care may be integral to the optimization of histone deacetylase inhibitor treatment in human patients.
Narver
Heather L
HL
Animal Care Division, National Institute of Neurological Disorders and Stroke, National Institute of Health, Johns Hopkins University, Baltimore, MD 21287, USA.
Kong
Lingling
L
Burnett
Barrington G
BG
Choe
Dong W
DW
Bosch-Marcé
Marta
M
Taye
Addis A
AA
Eckhaus
Michael A
MA
Sumner
Charlotte J
CJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009134:Muscular Atrophy, Spinal / Q000628:therapy*; D009336:Necrosis; D018529:Nutritional Support / Q000379:methods*; D016019:Survival Analysis; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D055533:Survival of Motor Neuron 1 Protein; C012589:trichostatin A