Neuropathy is a major cause of morbidity and mortality in individuals with diabetes, with no effective therapy to alter the inevitable progression of nerve damage. We hypothesized that mesenchymal stroma cell-like populations, that are characterized as immune modulators also have the potential of inducing angiogenesis and neurite outgrowth, might be useful in treating diabetic peripheral neuropathy (DPN). The aims of this study were to investigate the efficacy and safety of mesenchymal stem cell-like product (PDA-002) in treating DPN. A phase-2 randomized placebo-controlled trial was conducted in 26 patients with DPN. Treatment consisted of three rounds of intramuscular injections in one lower limb using one of the three randomized treatment arms PDA-002 (low-dose 3 × 10⁶ cells), PDA-002 (high-dose 30 × 10⁶ cells), or placebo. Three treatments per patient occurred on days 1, 29, and 57. Study endpoints included efficacy and safety of PDA-002 in treating DPN in both lower extremities following unilateral local injection. Outcome measures included intra-epidermal nerve fiber density (IENFD) up to 1 year from the day of treatment with 6-month as the primary outcome measurement. In this phase 2 study of DPN, PDA-002 was well tolerated in both doses. No significant changes were noted in IENFD in both the treated and untreated leg in the NIS-LL, NTSS-6, or UENS. Mesenchymal stem cells represent a novel mechanism for treating diabetic neuropathy and are well tolerated. Preliminary results highlight the need of further investigation of PDA-001 as a disease modifying agent for treatment of DPN.

中文翻译：

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调查 PDA-002 在糖尿病周围神经病变中的安全性和有效性的 2a 期随机对照研究

神经病变是糖尿病患者发病率和死亡率的主要原因，目前还没有有效的治疗方法来改变不可避免的神经损伤进展。我们假设以免疫调节剂为特征的间充质基质细胞样细胞群也具有诱导血管生成和神经突长出的潜力，可能有助于治疗糖尿病周围神经病变 (DPN)。本研究的目的是探讨间充质干细胞样产品（PDA-002）治疗DPN的有效性和安全性。在 26 名 DPN 患者中进行了一项 2 期随机安慰剂对照试验。治疗包括使用三个随机治疗组 PDA-002（低剂量 3 × 10 ^{6 个}细胞）、PDA-002（高剂量 30 × 10^{6 个}细胞）或安慰剂。在第 1 天、第 29 天和第 57 天，每位患者进行了 3 次治疗。研究终点包括 PDA-002 在单侧局部注射后治疗双下肢 DPN 的有效性和安全性。结果测量包括从治疗之日起长达 1 年的表皮内神经纤维密度 (IENFD)，其中 6 个月作为主要结果测量。在这项 DPN 2 期研究中，两种剂量的 PDA-002 均具有良好的耐受性。在 NIS-LL、NTSS-6 或 UENS 中，治疗和未治疗腿的 IENFD 均未发现显着变化。间充质干细胞代表了一种治疗糖尿病性神经病变的新机制，并且耐受性良好。初步结果强调需要进一步研究 PDA-001 作为治疗 DPN 的疾病调节剂。