Table 2.
List of patient/clinical trials employing histone deacetylase inhibition in the treatment of spinal muscular atrophy (SMA). ClinicalTrial.gov registration is provided where available
| Study/publication name | Trial ID | RCT | Status | Inhibitor | Clinically relevant conclusions |
|---|---|---|---|---|---|
| Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy | NA | Yes | Completed | PB | PB was not effective at the regimen, schedule, and duration used in this study [112] |
| Quantification of SMN protein in leucocytes from spinal muscular atrophy patients: Effects of treatment with Valproic acid | NA | No | Completed | VPA | VPA treatment resulted in significantly increased SMN protein levels in 5/6 SMA patients [104] |
| Valproic acid treatment in six patients with spinal muscular atrophy | NA | No | Completed | VPA | No effect in 1 type III adolescent and 2 type II/II adults, but muscle strength increase in 2 type II/III and 1 type III [106] |
| Pilot trial of phenylbutyrate in spinal muscular atrophy | NA | No | Completed | PB | PB might be beneficial to SMA patients without producing any major side effect [111] |
| Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients | NA | No | Completed | PB | PB significantly increases SMN expression in leukocytes of SMA patients [110] |
| In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate | NA | No | Completed | VPA | 7 of 10 carriers demonstrated increased SMN messenger RNA (mRNA) and protein levels. SMN2 mRNA levels were elevated in 7 patients and unchanged or decreased in 13 patients [105] |
| Valproate may improve strength and function in patients with type III/ IV spinal muscle atrophy | NA | No | Completed | VPA | VPA was followed by a sustained increase in function and strength in a group of patients with SMA III/IV [107] |
| Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy | NCT00227266 | Yes | Completed | VPA | VPA in combination with L-carnitine is not effective in improving strength or function in SMA children [108, 109] |
| Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy | NCT00374075 | No | Completed | VPA | VPA appears safe and well-tolerated, but weight gain and carnitine depletion are likely to be significant confounding factors [114] |
| Clinical Trial of Sodium Phenylbutyrate in Children With Spinal Muscular Atrophy Type I (NPTUNE 02) | NCT00439218 | No | Terminated owing to slow recruitment | PB | NA |
| Clinical Trial of Sodium Phenylbutyrate in Children With Spinal Muscular Atrophy Types II or III (NPTUNE01) | NCT00439569 | No | Terminated owing to poor drug administration compliance | PB | NA |
| Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy (VALIANTSMA) | NCT00481013 | No | Completed | VPA | NA |
| Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy (STOPSMA) | NCT00528268 | No | Recruiting | PB | NA |
| CARNIVAL Type I: Valproic Acid and Carnitine in Infants With Spinal Muscular Atrophy (SMA) Type I | NCT00661453 | No | Completed | VPA | NA |
| Evaluation of the Muscle Strength and Motor Ability in Children With Spinal Muscle Atrophy(SMA) Treated With Valproic Acid | NCT01033331 | No | Completed | VPA | NA |
| Valproate and Levocarni ne in Children With Spinal Muscular Atrophy | NCT01671384 | No | Not yet recruiting | VPA | NA |
ID identification, RCT randomized controlled trial, SMN survival of motor neuron, VPA valproic acid, PB phenylbutyrate, NA not available