Living Cell Technologies Limited (LCT) announced results from a phase I/IIa clinical study of NTCELL, an experimental regenerative cell therapy being studied as a disease-modifying agent in Parkinson’s disease.

The study, conducted in four patients in New Zealand, met its primary endpoint of safety, showing NTCELL implantation was well tolerated, with no adverse events considered to be related to NTCELL. NTCELL implantation also improved clinical features of Parkinson’s disease in the four patients studied, as measured by validated neurological rating scales and questionnaires, with the improvement sustained at 26 weeks post-implant.

The study results will be presented at the 19th International Congress of Parkinson’s Disease and Movement Disorders in San Diego on Wednesday 17 June, by principal investigator Barry J. Snow, MBChB, FRACP, in a guided poster tour presentation. The poster will be available for viewing starting 15 June.

“Currently, clinicians are able to manage only symptoms in patients with Parkinson’s disease as there are no disease-modifying treatments available that can reverse the underlying progressive degeneration of neurons in the brain,” said Dr. Snow, a neurologist in the department of neurology at Auckland City Hospital and medical director of Adult Medical Services at the Auckland District Health Board.

“The positive clinical response observed in this small study of four patients is encouraging and I look forward to evaluating efficacy in a larger study.”

Ken Taylor, Ph.D., chief executive officer of LCT, said “NTCELL is the most advanced and only cellbased therapy currently in a clinical trial to target regeneration of brain cells in patients whose symptoms cannot be controlled by current therapies for Parkinson’s disease. While this regulatoryenabling study is small in scale, the secondary endpoint efficacy results are sufficiently encouraging to warrant further studies. We are advancing the clinical development of NTCELL and will use the results of this study to design a larger registration-enabling phase IIb study to evaluate its potential as a disease-modifying treatment for patients with Parkinson’s disease.”

LCT plans to initiate the confirmatory phase IIb study in the fourth quarter of 2015. The study will be led by Dr. Snow at Auckland City Hospital. The efficacy and safety endpoints will be the same as those evaluated in the phase I/IIa study.

The open-label phase I/IIa clinical study evaluated the safety and clinical effects of implantation of NTCELL, which contains specialised brain cells that produce cerebrospinal fluid (CSF) and neuroactive growth factors, into patients who had been diagnosed with Parkinson’s disease for at least five years and who no longer responded to current therapy. The study was conducted at Auckland City Hospital in four patients aged 59 to 68 years at the time of consent. NTCELL was injected under guidance by neuroimaging into the affected area of the brain where neural activity was substantially diminished or degenerated. No immunosuppressive drugs were used.

The primary endpoint of the study was the safety of NTCELL implantation, which was assessed by the occurrence of adverse events and serious adverse events, as well as clinical and laboratory evidence of porcine endogenous retrovirus (PERV) in study participants and their partners. The secondary endpoint was efficacy, which was measured by validated neurological rating scales and questionnaires, including the Unified Parkinson’s Disease Rating Scale (UPDRS), the Unified Dyskinesia Rating Scale (UDysRS) and the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39) score. These scales assessed improvements in patients’ movement abnormalities, other physical symptoms, well-being and ability to perform everyday tasks. PET scans were conducted to measure the effects of NTCELL on dopamine brain metabolism. The results at week 26 following implantation were compared with those at baseline.

In the study, NTCELL was well tolerated. There were no adverse events or serious adverse events related to NTCELL in any of the four patients. Eight adverse events occurred, all of which were considered to be related to the implant procedure and none to NTCELL. There was no clinical or laboratory evidence of PERV transmission in patients or their partners. MRIs showed no evidence of inflammation.

All four patients experienced sustained improvement in clinical features as seen in UPDRS, UDysRs and PDQ-39 scores at week 26 post-implant. The first patient treated continued to show improvement in neurological scores at 74 weeks post-implantation. In this study, PET scan results did not show any consistent changes in the uptake of fluorodopa and tetrabenazine in the four patients, suggesting that the mechanism of NTCELL is not likely due to a direct change in dopaminergic neurons.

NTCELL, a unique cell therapy, is an alginate coated capsule containing clusters of neonatal porcine choroid plexus cells that are sourced from a unique herd of designated pathogen-free pigs bred from stock originally discovered in the remote sub-Antarctic Auckland Islands. Choroid plexus cells are naturally occurring “support” cells for the brain and secrete CSF, which contains a range of factors that support nerve cell functions and protective enzymes that are crucial for nerve growth and healthy functioning. In NTCELL, the porcine choroid plexus cells are coated with LCT’s propriety technology Immupel to protect them from attack by the immune system. Therefore, no immunosuppressive regimen is required for treatment.

Following implantation into a damaged site within the brain, NTCELL functions as a neurochemical factory producing CSF and secreting multiple nerve growth factors that promote new central nervous system (CNS) growth and repair disease-induced nerve degeneration while potentially removing waste products such as amyloids and proteins.

NTCELL has the potential to treat neurodegenerative diseases because choroid plexus cells help produce CSF as well as a range of neurotrophins (nerve growth factors) that have been shown to protect against neuron (nerve) cell death in animal models of disease. NTCELL has been shown in preclinical studies to regenerate damaged tissue and restore function in animal models of Parkinson’s disease, stroke, Huntington’s disease, hearing loss and other non-neurological conditions, such as wound healing. In addition to Parkinson’s disease, NTCELL has the potential to be used in a number of other CNS indications, including Huntington’s, Alzheimer’s and motor neurone diseases including amyotrophic lateral sclerosis (ALS).

Parkinson’s disease is a progressive neurological condition characterised by a loss of brain cells that produce dopamine (a neurotransmitter that conveys messages between brain cells to ensure effective movement and planning of movement) and many other types of neurons. People with Parkinson’s disease experience reduced and slow movement (hypokinesia and bradykinesia), rigidity and tremors. Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting approximately 4 million people worldwide. The average age of onset is 60 years, and the incidence increases with age. Men are one and a half times more likely to have Parkinson's disease than women.

Current treatments for Parkinson’s disease are symptomatic and do not reverse or slow the degeneration of neurons in the brain. Most existing pharmaceutical treatment options focus on restoring the balance of dopamine and other neurotransmitters. The effectiveness of dopamine replacement therapy declines as the disease progresses. When dopamine treatments are no longer useful, some patients are treated with Deep Brain Stimulation (DBS), in which a medical device is surgically implanted in the brain in order to send electrical impulses to regions of the brain involved in the control of movement. While DBS leads to short-term symptomatic improvement, it does not impact disease progression and is not curative or neuroprotective.