Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients.
Spinal muscular atrophy (SMA) is caused by insufficient levels of survival motor neuron (SMN) protein. Recently, we found that sodium 4-phenylbutyrate (PB), a well-tolerated FDA approved drug, enhances SMN gene expression in vitro. We provide here the first evidence that oral administration of PB (triButyrate significantly increases SMN expression in leukocytes of SMA patients. This finding provides a strong rationale to further investigate the effects of PB as also supported by preliminary clinical data.
Brahe
Christina
C
Istituto di Genetica Medica, Università Cattolica S Cuore, Largo F Vito, 1, 00168 Rome, Italy. cbrahe@rm.unicatt.it
Vitali
Tiziana
T
Tiziano
Francesco D
FD
Angelozzi
Carla
C
Pinto
Anna Maria
AM
Borgo
Federica
F
Moscato
Umberto
U
Bertini
Enrico
E
Mercuri
Eugenio
E
Neri
Giovanni
G
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D009133:Muscular Atrophy / Q000188:drug therapy / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010654:Phenylbutyrates / Q000008:administration & dosage*; D010865:Pilot Projects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D055532:SMN Complex Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D010654:Phenylbutyrates; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins