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.

Varenicline improves motor and cognitive symptoms in early Huntington's disease.

The aim of this study was to describe the effects of varenicline, a smoking cessation aid that acts as a nicotinic agonist, on cognitive function in patients with early clinical Huntington's disease (HD) who were current smokers. Three gene-positive patients transitioning to symptomatic HD were evaluated using the Unified Huntington's Disease Rating Scale part I and III (motor and behavioral subscales) at baseline and after 4 weeks of treatment. Cognitive function was assessed using a touch screen computer-based neurocognitive test battery (IntegNeuro®). Varenicline (1 mg twice daily) significantly improved performance in executive function and emotional recognition tasks. Our case reports describe no clinically significant adverse effects and suggest that varenicline improves aspects of cognitive function in patients with early HD. A randomized controlled study is now underway.

The Appointment of a Huntington's Disease Nurse Specialist has Reduced Admission Rate and Improved Admission Quality.

We aimed to determine if the appointment of a Huntington's disease (HD) nurse specialist has influenced inpatient admission rates and admission quality at Auckland Hospital. We collated HD inpatient admission data for the 32 months before and after her appointment and compared the quality of cognition, mood, speech/swallowing and safety assessments between admissions where the nurse was and was not involved. After the appointment of the HD nurse there was a 51% reduction in average monthly HD admission rates (p = 0.0009). HD admissions specifically related to HD decreased by 54% (p = 0.005). There was also an improvement in the quality of admissions.

Temporal lobe resection for refractory temporal lobe epilepsy at Auckland Hospital.

AIMS: To analyse the long-term outcome of patients who underwent temporal lobe resection for intractable temporal lobe epilepsy at Auckland Hospital. METHODS: We performed a retrospective analysis of 176 patients who underwent temporal lobe resection at Auckland Hospital, New Zealand between 1987 and 2007. We had at least 1 year of follow-up on 174 patients. RESULTS: Overall 98/174 (56%) individuals were seizure-free at 1 year (Engel Class 1) with a marked improvement in quality of life. A further 61/174 (35%) had rare seizures or had significant improvement in seizure frequency (Engel Classes II or III). At last follow up (mean 4.3 years) 95/174 (55%) were seizure-free (Engel Class 1). Hippocampal sclerosis was the pathological finding in 129 patients. Surgical complications included 2 (1.1%) deaths, while 6 (3.4%) patients had symptomatic visual field defects, and 8 (4.5%) had other permanent neurological problems. A further 18 (10.3%) patients had temporary complications including infection, pulmonary embolus, and aseptic meningitis. New psychological symptoms occurred during the first year after surgery in 52% of 114 patients for whom we had detailed psychiatric assessments. CONCLUSION: Temporal lobe resection is effective in controlling medically intractable seizures, but there are potentially serious complications that need to be considered when counselling patients for such a procedure.