背景:Phelan-McDermid综合征(PMS),也被称为22Q13。3缺失综合征,是一种罕见的神经发育综合征,全球报告了约2,800名患者。先前的初步研究表明,IGF-1可以显着改善患者的社会障碍和限制性行为。然而,像中国这样的发展中国家的大多数患者负担不起使用IGF-1的高昂费用。我们的研究小组推测rhGH可能作为PMS的低成本和更容易获得的治疗方法。因此,这个开放标签的目的,cross-over,初步研究旨在进一步研究rhGH在PMS患者中的安全性和有效性。
方法:共有6名患有PMS的儿童参加了这个开放标签,cross-over,试点研究。将儿童随机分为两组。A组接受安慰剂,然后接受rhGH,B组先用rhGH治疗。在研究阶段I之前和阶段I干预后3个月对患者进行神经心理和行为评估。经过4周的冲洗期,这些评估在II期研究前和II期干预后3个月再次进行.在初步研究的干预阶段,还每月评估血清胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白(IGFBP)-3。
结果:与安慰剂相比,rhGH治疗显著降低了GDS的子量表评分(P<0.0085),有改善GDS总分的趋势(P<0.05),rhGH治疗3个月后,SC-ABC的总分和子量表得分显着降低(P<0.0085)。与基线相比也观察到类似的结果。与基线相比,rhGH治疗3个月后,血清IGF-1和IGFBP-3水平显着升高(P<0.05),而安慰剂组对血清IGF-1和IGFBP-3无显著影响(P>0.05)。一名儿童在第一次rhGH治疗后的第二天出现皮肤过敏,后来解决了。
结论:总之,这项涉及6名PMS儿童患者的初步研究表明,rhGH对PMS有积极的治疗作用。这些结果鼓励了大规模的事业,随机安慰剂对照试验最终证明rhGH在PMS中的疗效和耐受性,从而将其推广为低成本,PMS更容易获得的治疗,与IGF-1相比。
BACKGROUND: Phelan-McDermid syndrome (PMS), also known as the 22q13. 3 deletion syndrome, is a rare neurodevelopmental syndrome with approximately 2,800 patients reported worldwide. Previous pilot
study demonstrated that IGF-1 could significantly improve in both social impairment and restrictive behaviors of the patients. However, most of the patients in the developing countries like China cannot afford the high cost of using IGF-1. Our research team speculated that rhGH might serve as a low-cost and more accessible treatment for PMS. Therefore, the purpose of this open-label, cross-over, pilot
study was to further investigate the safety and efficiency of rhGH in patients with PMS.
METHODS: A total of six children with PMS were enrolled in in this open-label, cross-over, pilot study. The children were randomly divided into two different groups. Group A received placebo followed by rhGH, while group B was treated with rhGH first. Neuropsychological and behavior assessments of the patients were performed before the stage I of
study and 3 months after the intervention of stage I. After a 4-week period of washout, these assessments were conducted again before the stage II of
study and 3 months after the intervention of stage II. Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding-protein (IGFBP)-3 were also evaluated monthly during the intervention phases of the pilot study.
RESULTS: Compared with the placebo, rhGH treatment significantly decreased subscale scores of GDS (P < 0.0085) and trended to improve the total scores of GDS (P < 0.05), while the total scores and subscale scores of SC-ABC significantly decreased (P < 0.0085) following 3-months rhGH treatment. The similar results were also observed in comparison with baseline. Compared with the baseline, the level of serum IGF-1 and IGFBP-3 increased significantly (P < 0.05) following 3-months rhGH treatment, while the placebo group had no significant impact on serum IGF-1 and IGFBP-3 (P > 0.05). One child developed skin allergy the day after the first rhGH treatment, which were resolved later.
CONCLUSIONS: In summary, this pilot study involving six PMS children patients reveals that rhGH has a positive treatment effect on PMS. These results encourage the undertaking of a large, randomized placebo-controlled
trial to conclusively prove rhGH efficacy and tolerability in PMS, thereby promoting it as a low-cost, more accessible treatment for PMS, as compared to IGF-1.