Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Neurology. 2013 Jul 30;81(5):427-30. doi: 10.1212/WNL.0b013e31829d85c0. Epub 2013 Jun 28.
The objective of this study was to retrospectively evaluate neurologic status pre- and posttreatment with the oral farnesyltransferase inhibitor lonafarnib in children with Hutchinson-Gilford progeria syndrome (HGPS), a rare, fatal disorder of segmental premature aging that results in early death by myocardial infarction or stroke.
The primary outcome measure for intervention with lonafarnib was to assess increase over pretherapy in estimated annual rate of weight gain. In this study, neurologic signs and symptoms were compared pre- and posttreatment with lonafarnib.
Twenty-six participants were treated for a minimum of 2 years. Frequency of clinical strokes, headaches, and seizures was reduced from pretrial rates. Three patients with a history of frequent TIAs and average clinical stroke frequency of 1.75/year during the year before treatment experienced no new events during treatment. One patient with a history of stroke died due to large-vessel hemispheric stroke after 5 months on treatment. Headache prevalence and frequency were reduced. Four patients exhibited pretherapy seizures and no patients experienced recurrent or new-onset seizures.
This study provides preliminary evidence that lonafarnib therapy may improve neurologic status of children with HGPS. To address this question, we have incorporated prospective neuroimaging and neurologic assessments as measures in subsequent studies involving children with HGPS.
This study provides Class IV evidence that lonafarnib 115-150 mg/m(2) for 24 to 29 months reduces the prevalence of stroke and TIA and the prevalence and frequency of headache over the treatment period.
本研究旨在回顾性评估 Hutchinson-Gilford 早衰综合征（HGPS）患儿经口服法尼基转移酶抑制剂 lonafarnib 治疗前后的神经状态。HGPS 是一种罕见的致命性节段性过早衰老疾病，可导致心肌梗死或中风而早期死亡。
lonafarnib 干预的主要结局测量指标是评估治疗前估计的年体重增长率增加。在这项研究中，比较了 lonafarnib 治疗前后的神经症状和体征。
26 名参与者至少接受了 2 年的治疗。与治疗前相比，临床中风、头痛和癫痫发作的频率有所降低。3 名有频繁 TIA 病史且治疗前平均每年临床中风频率为 1.75 次的患者在治疗期间未发生新事件。1 名有中风病史的患者在治疗后 5 个月因大血管半球性中风死亡。头痛的发生率和频率均有所降低。4 名患者出现治疗前癫痫发作，无患者出现复发性或新发性癫痫发作。
本研究初步证明 lonafarnib 治疗可能改善 HGPS 患儿的神经状态。为了解决这个问题，我们已经将前瞻性神经影像学和神经评估纳入了随后涉及 HGPS 患儿的研究中作为措施。
本研究提供了 IV 级证据，表明 lonafarnib 115-150mg/m²，持续 24 至 29 个月，可降低中风和 TIA 的发生率，以及治疗期间头痛的发生率和频率。
