Phase 2a randomized controlled study investigating the safety and efficacy of PDA‐002 in diabetic peripheral neuropathy

Abstract

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 placebocontrolled 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 Â 10 6 cells), PDA-002 (high-dose 30 Â 10 6 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. K E Y W O R D S diabetes, diabetic peripheral neuropathy, neuropathy, stem cells 1 | INTRODUCTION Diabetes mellitus (DM) is a multi-organ system disease affecting the nerves, kidneys, eyes, and blood vessels. The estimated incidence of diabetes in the United States (US) exceeds 1.9 million new cases annually, with an overall prevalence of over 25 million people or 8.3% of the nation's population and approximately 50% of those with diabetes will have neurological complications. 1 Type 2 diabetes is by far the most common, accounting for 90% of all individuals with diabetes. 1The most common manifestation of diabetic peripheral neuropathy (DPN) is a distal symmetric polyneuropathy which initially affects the distal lower extremities and gradually ascends and can ultimately progress to sensory loss in the classical "stocking-glove" distribution. 2Abbreviations: CFB, change from baseline; DPN, diabetic peripheral neuropathy; IENFD, intra-epidermal nerve fiber density; NFD, nerve fiber density; NIS-LL, neurological impairment score of the lower limb; NTSS-6, 6-item neuropathy total symptom score; PDAC, placenta-derived adherent cells; UENS, Utah early neuropathy scale.