We’re now seeing cell-based therapies being investigated for a number of disorders, with neurodegenerative diseases being no exception. In 2015, the first-in-human clinical study of neural stem cells in patients with Parkinson’s disease (PD) began, with promising 6-month results now being reported. In light of this, we spoke to Russell Kern, CSO at International Stem Cell Corporation (ISCO; CA, USA), which developed the ISC-hpNSC cell line being used in the trial. In this interview, Russell tells us more about the trial, next steps, and how these cell lines are also being used to tackle other conditions including traumatic brain injury (TBI).
The ISCO is pioneering the use of ISC-hpNSCs in a number of trials – can you tell us about the first-in-human clinical study of neural stem cells in patients with PD?
ISCO received approval of the world’s first human pluripotent stem cell-based therapy for PD. This is an open-label, single center, uncontrolled Phase I study evaluating the safety and tolerability of intracranial transplantation of ISC-hpNSC in PD patients. This study is conducted at the Royal Melbourne Hospital in Australia and the principal investigator is Andrew Evans (Royal Melbourne Hospital, Australia). Three different dose regimens of ISC-hpNSC (30, 50 and 70 million cells) are tested in 12 patients divided into three cohorts of four patients each. So far four patients from the first cohort and three patients from the second cohort have been dosed with 30 and 50 million cells, respectively. No serious adverse events associated with ISC-hpNSC have been detected thus far.
Six month interim data from the first cohort shows improvements of 24% in the % OFF-Time and 19% in the % ON-Time without dyskinesia. There was an improvement of 35% in the Beck Depression Inventory and 33% in the Emotional Wellbeing dimension of the Parkinson’s Disease Quality of Life Score-39 (PDQ-39). The PDQ-39 score improved in several other dimensions including activities of daily living, mobility, bodily discomfort and cognitive impairment. Impulsive and compulsive disorders were diminished, as demonstrated by the 53% reduction in the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale. These results are very encouraging because the first dose was sub-therapeutic and was used to test the safety and feasibility of the procedure. Patients from the second and third cohort receive higher cell doses shown to be therapeutic in our preclinical studies.
The next step now is to complete the Phase I study and analyze all the safety and efficacy data. After that, we are planning to file an IND to the US FDA to conduct a double-blind, placebo-controlled, multi-center Phase II study in PD patients with sites in the USA and Australia.
You’re also investigating the use of these cells to treat TBI – can you tell us more about this?
Yes, the beauty about neural stem cells is that they can be used to treat a multitude of neurological indications because of their neuroregenerative, neurotrophic and neuro-immunomodulative properties. We have conducted preclinical studies and have found that intracranial transplantation of ISC-hpNSC significantly improves cognitive performance, locomotion, and neurological function in rodents with TBI. We are planning to file an IND to the US FDA to conduct a double-blind, placebo-controlled, multi-center Phase II study in TBI patients with sites in the USA and Australia.
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What are the most significant challenges that you’ve come up against in the ISC-hpNSC trials? How do you hope to overcome these?
The most significant challenge that we are currently facing in our ISC-hpNSC trial in PD is the recruitment of patients with particular characteristics. We plan to overcome this in our Phase II study by opening multiple sites in the USA and Australia to increase the recruitment rates.
More generally, what do you see as the biggest questions to be addressed in the field of cell therapy for neurological diseases and injury?
Some of the biggest questions to be addressed in the field of cell therapy for neurological diseases and injury are the biodistribution, fate and functional activity of the cells once implanted into patients.
Do you think we could one day see stem cell therapy as a standard treatment for PD?
Yes, I believe stem cell therapy holds great promise and can one day be a standard treatment for PD. Current treatments only address symptoms and do not rescue the damaged nigrostriatal pathway. Based on our preclinical studies and the previous clinical studies conducted with fetal tissue, we know that stem cel- based therapies have the potential to re-innervate the striatum, replenish some of the lost dopaminergic neurons and provide symptomatic relief for several years.
Finally, where you do you hope we can be in 5–10 years’ time?
In the next 5–10 years’ time, we would like to see our cell based therapies commercialized and be used as a standard treatment for different neurological indications. A one-time surgical intervention has the potential to significantly improve people’s lives and we are working very diligently to reach that goal and make this treatment available to millions of patients.
Biography – Russell Kern
Russell’s background is in medical genetics, embryology and stem cell biology and he holds a Ph.D. degree in Human Physiology from the Russian Academy of Medical Sciences (Moscow, Russia). Russell has broad expertise in neuroscience, and during his graduate work he was part of the team, along with scientists from the NYU Medical School (NY, USA), that elucidated some of the physiological changes that occur in the brains of PD patients. Russell is now Chief Scientific Officer at ISCO and oversees all R&D programs including stem cell derivation, differentiation and pre-clinical and clinical studies. He has been with ISCO since 2009 and has overseen the development of human parthenogenetic stem cell derived neural stem cells (ISC-hpNSC) from its early discovery stage to its clinical translation.