A long-term follow-up of safety and clinical efficacy of NTCELL® [Immunoprotected (Alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease.

INTRODUCTION: In 2019, we published the results of a Phase IIb randomized controlled trial of putaminal encapsulated porcine choroid plexus cell (termed NTCELL®) administration in patients with Parkinson's disease. This study failed to meet its primary efficacy end-point of a change in UPDRS part III score in the 'off' state at 26-weeks post-implant. However, a number of secondary end-points reached statistical significance. We questioned whether with longer follow-up, clinically significant improvements would be observed. For this reason, we decided to follow-up all patients periodically to week 104. Herein, we report the results of this long-term follow-up. METHODS: All 18 patients included in the original study were periodically re-assessed at weeks 52, 78 and 104 post-implant. At each time-point, motor and non-motor function, quality of life and levodopa equivalent daily dose was assessed using a standardized testing battery. RESULTS: At week 104, no significant differences in UPDRS part III scores in the 'off' state were observed in any of the treatment groups compared to baseline. Only a single serious adverse event - hospitalisation due to Parkinson's disease rigidity not responding to changes in medications - was considered potentially related to the implant procedure. There was no evidence of xenogeneic viral transmission. CONCLUSION: Un-blinded, long-duration follow-up to week 104 post-implantation showed no evidence that putaminal NTCELL® administration produces significant clinical benefit in patients with moderately advanced Parkinson's disease.

A phase IIb, randomised, double-blind, placebo-controlled, dose-ranging investigation of the safety and efficacy of NTCELL® [immunoprotected (alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease.

INTRODUCTION: Regenerative therapies in Parkinson's disease aim to slow neurodegeneration and re-establish damaged neuronal circuitry. Neurotrophins are potent endogenous regulators of neuronal survival, development and regeneration. They represent an attractive regenerative treatment option in Parkinson's disease. Porcine choroid plexus produces a number of neurotrophins, and can be safely delivered to the striatum in an encapsulated formulation (termed NTCELL®) to protect them from immune attack. NTCELL® has shown regenerative potential in animal models of stroke, Huntington's disease and Parkinson's disease. Following promising results from an initial open label safety study of intra-striatal delivery of NTCELL® in human subjects, we sought to specifically investigate the safety and efficacy of NTCELL® for the treatment of Parkinson's disease. METHODS: 18 patients aged 56-65 years with idiopathic Parkinson's disease of at least 5 years duration were randomised to receive either sham surgery (general anaesthesia and partial thickness burr holes) or intra-striatal delivery of NTCELL® (the 3 groups in the treatment arm receiving incremental NTCELL® doses). RESULTS: At 26 weeks, we found no significant difference in total UPDRS scores ('on' and 'off'), UPDRS motor scores ('on' and 'off'), PDQ-39, UDysRS, timed walk or modified Hoehn and Yahr stage between patients implanted with NTCELL® and patients undergoing sham procedure. There were no serious adverse events or xenogeneic viral transmission during the study. CONCLUSION: The study did not meet its primary efficacy end-point of a change in UPDRS at 26 weeks post-intervention compared with baseline. Stereotactic NTCELL® implantation was safe and well tolerated.

Analysis of Outcomes of Multidisciplinary Management of Gliosarcoma: A Single-Center Study, 2000-2013.

BACKGROUND: Gliosarcoma is a rare tumor of the central nervous system with a reported incidence of ∼2%-8% of all gliomas. We reviewed the outcomes of patients treated at our institution over a 14-year period from 2000 to 2013 to characterize overall survival (OS) and progression-free survival as well as to elucidate the additive effect of chemoradiotherapy. METHODS: From January 1, 2000 to December 31, 2013, we retrospectively reviewed the clinical notes of all patients treated at our institution with a histopathologic diagnosis of gliosarcoma. This review yielded 21 patients whose clinicoradiologic data were analyzed with respect to age, sex, ethnicity, preoperative/postoperative Glasgow Coma Scale and Karnofsky Performance Scale, location, extent of resection, methylguanine DNA methyl transferase methylation status, and administration of adjuvant therapy. RESULTS: The median age was 58 years (range, 40-80 years) with a male preponderance (1.6:1). Tumor location was mainly temporal (n = 6) but also parietal (n = 5), frontal (n = 4), multilobar (n = 4), and cerebellar (n = 1). Surgical resection was deemed to be total in 15 patients and subtotal in 6 patients. Methylguanine DNA methyl transferase methylation status was available for only 5 patients, with a methylation rate of 60% (3/5) and no impact on survival. Nine patients received both radiotherapy and chemotherapy (OS, 7.9 months), 7 received radiotherapy only (OS, 5.7 months), and 5 patients received no adjuvant therapy (OS, 1.4 months). The overall median survival was 5.7 months (range, 1-21.5 months) and median progression-free survival was 5 months (range, 1.4-12.4 months). CONCLUSIONS: Despite an overall poor prognosis, a multimodality approach aiming for complete resection followed by radiotherapy and chemotherapy appears to be associated with better outcomes.