A Randomized Controlled Trial of SGS-742, a γ-aminobutyric acid B (GABA-B) Receptor Antagonist, for Succinic Semialdehyde Dehydrogenase Deficiency

被引：9

作者：

Schreiber, John M. ^{[1
,2
]}

Wiggs, Edythe ^{[3
]}

Cuento, Rose ^{[3
,4
]}

Norato, Gina ^{[3
]}

Dustin, Irene H. ^{[1
]}

Rolinski, Rachel ^{[1
]}

Austermuehle, Alison ^{[1
]}

Zhou, Xiangping ^{[1
]}

Inati, Sara K. ^{[3
]}

Gibson, K. Michael ^{[5
]}

Pearl, Phillip L. ^{[6
]}

Theodore, William H. ^{[1
]}

机构：

[1] NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 7D-43, Bethesda, MD 20892 USA

[2] Childrens Natl Hosp, Div Epilepsy Neurophysiol & Crit Care Neurol, Washington, DC USA

[3] NINDS, Off Clin Director, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[4] NINDS, Clin Trials Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[5] Washington State Univ, Dept Pharmacotherapy, Coll Pharm & Pharmaceut Sci, Spokane, WA USA

[6] Boston Childrens Hosp, Dept Epilepsy & Clin Neurophysiol, Boston, MA USA

来源：

JOURNAL OF CHILD NEUROLOGY | 2021年 / 36卷 / 13-14期

基金：

美国国家卫生研究院;

关键词：

cognition; efficacy; inborn errors of metabolism; neurodevelopment; treatment; epilepsy; HYDROXYBUTYRIC ACID; OXIDATIVE STRESS; MOTOR CORTEX; BINDING; INHIBITION; DISORDER; PATIENT; SGS742; MICE; WEAK;

D O I：

10.1177/08830738211012804

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

We examined safety, tolerability, and efficacy of SGS-742, a gamma-aminobutyric acid B (GABA-B) receptor antagonist, in patients with succinic semialdehyde dehydrogenase deficiency. This was a single-center randomized, double-blind crossover phase II clinical trial of SGS-742 versus placebo in patients with succinic semialdehyde dehydrogenase deficiency. Procedures included transcranial magnetic stimulation and the Adaptive Behavior Assessment Scale. Nineteen subjects were consented and enrolled; the mean age was 14.0 +/- 7.5 years and 11 (58%) were female. We did not find a significant effect of SGS-742 on the Adaptive Behavior Assessment Scale score, motor threshold, and paired-pulse stimulation. The difference in recruitment curve slopes between treatment groups was 0.003 (P = .09). There was no significant difference in incidence of adverse effects between drug and placebo arms. SGS-742 failed to produce improved cognition and normalization of cortical excitability as measured by the Adaptive Behavior Assessment Scale and transcranial magnetic stimulation. Our data do not support the current use of SGS-742 in succinic semialdehyde dehydrogenase deficiency. Trial registry number NCT02019667. Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency.

引用

页码：1189 / 1199

页数：11