PDF(Pubmed)
Abstract：
UNASSIGNED: To evaluate the interim feasibility, safety and clinical measures data of direct delivery of regenerating peripheral nerve tissue (PNT) to the substantia nigra (SN) in participants with Parkinson\'s disease (PD).
UNASSIGNED: Eighteen (13 men/5 women) participants were unilaterally implanted with PNT to the SN, contralateral to the most affected side during the same surgery they were receiving deep brain stimulation (DBS) surgery. Autologous PNT was collected from the sural nerve. Participants were followed for safety and clinical outcomes for 2 years (including off-state Unified Parkinson\'s Disease Rating Scale (UPDRS) Part III assessments) with study visits every 6 months.
UNASSIGNED: All 18 participants scheduled to receive PNT implantation received targeted delivery to the SN in addition to their DBS. All subjects were discharged the following day except for two: post-op day 2; post-op day 3. The most common study-related adverse events were hypoaesthesia and hyperaesthesias to the lateral aspect of the foot and ankle of the biopsied nerve (6 of 18 participants experienced). Clinical measures did not identify any hastening of PD measures providing evidence of safety and tolerability. Off-state UPDRS Part III mean difference scores were reduced at 12 months compared with baseline (difference=-8.1, 95% CI -2.4 to -13.9 points, p=0.005). No complications involving dyskinesias were observed.
UNASSIGNED: Targeting the SN for direct delivery of PNT was feasible with no serious adverse events related to the study intervention. Interim clinical outcomes show promising results meriting continued examination of this investigational approach.
UNASSIGNED: NCT02369003.
UNASSIGNED: Eighteen (13 men/5 women) participants were unilaterally implanted with PNT to the SN, contralateral to the most affected side during the same surgery they were receiving deep brain stimulation (DBS) surgery. Autologous PNT was collected from the sural nerve. Participants were followed for safety and clinical outcomes for 2 years (including off-state Unified Parkinson\'s Disease Rating Scale (UPDRS) Part III assessments) with study visits every 6 months.
UNASSIGNED: All 18 participants scheduled to receive PNT implantation received targeted delivery to the SN in addition to their DBS. All subjects were discharged the following day except for two: post-op day 2; post-op day 3. The most common study-related adverse events were hypoaesthesia and hyperaesthesias to the lateral aspect of the foot and ankle of the biopsied nerve (6 of 18 participants experienced). Clinical measures did not identify any hastening of PD measures providing evidence of safety and tolerability. Off-state UPDRS Part III mean difference scores were reduced at 12 months compared with baseline (difference=-8.1, 95% CI -2.4 to -13.9 points, p=0.005). No complications involving dyskinesias were observed.
UNASSIGNED: Targeting the SN for direct delivery of PNT was feasible with no serious adverse events related to the study intervention. Interim clinical outcomes show promising results meriting continued examination of this investigational approach.
UNASSIGNED: NCT02369003.
摘要：
■为了评估临时可行性，帕金森病（PD）参与者将再生周围神经组织（PNT）直接递送至黑质（SN）的安全性和临床措施数据。
■18名（13名男性/5名女性）参与者被单侧植入PNT到SN，在接受深部脑刺激（DBS）手术的同一手术中，对侧至受影响最严重的一侧。从腓肠神经收集自体PNT。对参与者进行2年的安全性和临床结果随访（包括州外统一帕金森病评定量表（UPDRS）第三部分评估），每6个月进行一次研究访视。
■除DBS外，计划接受PNT植入的所有18名参与者均接受了向SN的靶向递送。所有受试者在第二天出院,除了两个:术后第2天;术后第3天。最常见的与研究相关的不良事件是对活检神经的足踝外侧的感觉减退和感觉过度（18名参与者中有6名经历）。临床措施未发现PD措施的任何加速提供安全性和耐受性的证据。与基线相比，离州UPDRS第三部分在12个月时平均差异得分降低（差异=-8.1，95％CI-2.4至-13.9分，p=0.005)。未观察到涉及运动障碍的并发症。
■针对SN直接递送PNT是可行的，没有与研究干预相关的严重不良事件。中期临床结果显示有希望的结果，值得继续检查这种研究方法。
■NCT02369003。
■18名（13名男性/5名女性）参与者被单侧植入PNT到SN，在接受深部脑刺激（DBS）手术的同一手术中，对侧至受影响最严重的一侧。从腓肠神经收集自体PNT。对参与者进行2年的安全性和临床结果随访（包括州外统一帕金森病评定量表（UPDRS）第三部分评估），每6个月进行一次研究访视。
■除DBS外，计划接受PNT植入的所有18名参与者均接受了向SN的靶向递送。所有受试者在第二天出院,除了两个:术后第2天;术后第3天。最常见的与研究相关的不良事件是对活检神经的足踝外侧的感觉减退和感觉过度（18名参与者中有6名经历）。临床措施未发现PD措施的任何加速提供安全性和耐受性的证据。与基线相比，离州UPDRS第三部分在12个月时平均差异得分降低（差异=-8.1，95％CI-2.4至-13.9分，p=0.005)。未观察到涉及运动障碍的并发症。
■针对SN直接递送PNT是可行的，没有与研究干预相关的严重不良事件。中期临床结果显示有希望的结果，值得继续检查这种研究方法。
■NCT02369003。
