Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
BMJ Open Diabetes Res Care. 2021 Oct;9(1). doi: 10.1136/bmjdrc-2021-002442.
Experimentally, gamma-aminobutyric acid (GABA) has been found to exert immune-modulatory effects and induce beta-cell regeneration, which make it a highly interesting substance candidate for the treatment of type 1 diabetes (T1D). In many countries, including those in the European Union, GABA is considered a pharmaceutical drug. We have therefore conducted a safety and dose escalation trial with the first controlled-release formulation of GABA, Remygen (Diamyd Medical).
Six adult male subjects with long-standing T1D (age 24.8±1.5 years, disease duration 14.7±2.2 years) were enrolled in an 11-day dose escalation trial with a controlled-release formulation of GABA, Remygen. Pharmacokinetics, glucose control and hormonal counter-regulatory response during hypoglycemic clamps were evaluated at every dose increase (200 mg, 600 mg and 1200 mg).
During the trial there were no serious and only a few, transient, adverse events reported. Without treatment, the counter-regulatory hormone response to hypoglycemia was severely blunted. Intake of 600 mg GABA more than doubled the glucagon, epinephrine, growth hormone and cortisol responses to hypoglycemia.
We find that the GABA treatment was well tolerated and established a counter-regulatory response to hypoglycemia in long-standing T1D. Further studies regarding not only the clinical potential of Remygen for beta-cell regeneration but also its potential use as hypoglycemic prophylaxis are warranted.
NCT03635437 and EudraCT2018-001115-73.
实验发现，γ-氨基丁酸（GABA）具有免疫调节作用，并能诱导β细胞再生，这使其成为 1 型糖尿病（T1D）治疗的极具潜力的候选物质。在许多国家，包括欧盟国家，GABA 都被视为一种药物。因此，我们对首款 GABA 控释制剂 Remygen（Diamyd Medical）进行了安全性和剂量递增试验。
6 名患有长期 T1D 的成年男性受试者（年龄 24.8±1.5 岁，病程 14.7±2.2 年）参与了一项 GABA 控释制剂的 11 天剂量递增试验。在每次剂量增加（200mg、600mg 和 1200mg）时，评估药代动力学、血糖控制和低血糖钳夹期间的激素反调节反应。
在试验期间，仅报告了少数几起轻微且短暂的不良事件，没有严重不良事件。未经治疗时，低血糖的激素反调节反应严重减弱。摄入 600mg GABA 可使胰高血糖素、肾上腺素、生长激素和皮质醇对低血糖的反应增加一倍以上。
我们发现 GABA 治疗具有良好的耐受性，并在长期 T1D 中建立了对低血糖的反调节反应。进一步的研究不仅需要关注 Remygen 在β细胞再生方面的临床潜力，还需要关注其作为低血糖预防的潜在用途。
NCT03635437 和 EudraCT2018-001115-73。
