International Stem Cell Corporation Completes Dosing of Second Cohort in Parkinson's Disease Trial

International Stem Cell Corporation recently announced the eighth participant, which completes the dosing of the second cohort of the clinical trial for Parkinson’s disease, was successfully transplanted with ISC-hpNSC cells at the Royal Melbourne Hospital in Melbourne, Australia.

ISCO’s Executive Vice President and Chief Scientific Officer Russell Kern, PhD, commented “We are pleased to provide an update with the progress of our Parkinson’s disease clinical trial. The completion of the second cohort of patients who received 50 million ISC-hpNSC cells, which represents a biologically active dose in our preclinical studies, is a significant milestone for ISCO. The data from the first cohort of our groundbreaking therapy is already indicating safety and early signals of efficacy.”

Recently, ISCO announced its interim results of this clinical study at the Society of Neurosciences Annual Meeting held in Washington DC. The % OFF-Time, which refers to the time of day when levodopa medication is not performing optimally and Parkinson’s disease symptoms return, decreased an average of 24% for the first cohort at six months post-transplantation. The % ON-Time without dyskinesia, which refers to the time of day when levodopa medication is performing optimally without dyskinesia, increased an average of 19% for the first cohort during the same period. 100% of the patients improved their mood six months post-transplantation with an average 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). 100% of patients improved or retained the same cognitive abilities with an average improvement of 14% in the Cognitive Impairment dimension of the PDQ-39.

The introduction of levodopa more than 40 years ago revolutionized the treatment of Parkinson’s disease. While no drug has been shown to slow the progression of the disease itself, levodopa has proven to significantly reduce Parkinson’s disease symptoms with most patients. However, there are no approved treatments that can fully restore damaged dopaminergic neurons in the human brain. The death of these neurons is what induces the motor symptoms most commonly associated with Parkinson’s disease, including stiffness, slowness, tremors and posture instability. Based on ISCO’s preclinical research, ISC-hpNSC has the potential to provide neurotrophic support and neuroregeneration to the affected tissues of the recipient brain. ISC-hpNSC is the world’s first pluripotent stem cell-based therapy for Parkinson’s disease and if successful, it would represent a paradigm shift in the treatment of this life-altering disease.

The Phase I clinical study is a dose escalation safety and preliminary efficacy study of ISC-hpNSC, intracranially transplanted into patients with moderate Parkinson’s disease. The open-label, single center, uncontrolled clinical trial will evaluate three different dose regimens of 30,000,000 to 70,000,000 neural cells. A total of 12 participants with moderate-to-severe Parkinson’s disease will be treated. Following transplantation, the patients will be monitored for 12 months at specified intervals to evaluate the safety and biologic activity of ISC-hpNSC. A PET scan will be performed at baseline, as part of the screening assessment, and at 6 and 12 months after surgical intervention. Clinical responses compared to baseline after the administration of ISC-hpNSC will be evaluated using various neurological assessments such as Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr and other rating scales. An extension phase of the study will evaluate patients every 6 months for 5 additional years.

Parkinson’s disease is a degenerative disorder of the central nervous system mainly affecting the motor system. The motor symptoms of Parkinson’s disease result from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain. Early in the course of the disease, the most obvious symptoms are movement-related. These symptoms include shaking, rigidity, slowness of movement and difficulty with walking and gait. Later, thinking and behavioral problems may arise, with dementia commonly occurring in the advanced stages of the disease, and depression as the most common psychiatric symptom. Parkinson’s disease is more common in people over the age of 50.

There are no approved treatments that restore the damaged dopaminergic neurons. Medications typically used in the treatment of Parkinson’s disease, levodopa and dopamine agonists, improve the early symptoms of the disease. As the disease progresses and dopaminergic neurons continue to be lost, the drugs eventually become ineffective, while at the same time frequently producing a complication marked by involuntary writhing movements. There are over 10 million people afflicted by Parkinson’s disease worldwide. In 2013 Parkinson’s disease resulted in about 103,000 deaths globally, up from 44,000 deaths in 1990.

International Stem Cell Corporation’s proprietary ISC-hpNSC consists of a highly pure population of neural stem cells derived from human parthenogenetic stem cells. ISC-hpNSC is a suspension of clinical grade cells manufactured under cGMP conditions that have undergone stringent quality control measures and are clear of any microbial and viral contaminants. Preclinical studies in rodents and non-human primates have shown improvement in Parkinson’s disease symptoms and increase in brain dopamine levels following the intracranial administration of ISC-hpNSC. ISC-hpNSC provides neurotrophic support and neuroregeneration to the dying dopaminergic neurons of the recipient Parkinson’s disease brain. Additionally, ISC-hpNSC is safe, well tolerated and does not cause adverse events such as dyskinesia, systemic toxicity or tumors in preclinical models. International Stem Cell Corporation believes that ISC-hpNSC may have broad therapeutic applications for many neurological diseases affecting the brain, the spinal cord and the eye.

International Stem Cell Corporation (ISCO) is focused on the therapeutic applications of human parthenogenetic stem cells (hpSCs) and the development and commercialization of cell-based research and cosmetic products. ISCO’s core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenetic, homozygous stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals of differing genders, ages and racial background with minimal immune rejection after transplantation. hpSCs offer the potential to create the first true stem cell bank, UniStemCell. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology (www.lifelinecelltech.com), and stem cell-based skin care products through its subsidiary Lifeline Skin Care (www.lifelineskincare.com). More information is available atwww.internationalstemcell.com.