Positive animal data reported by International Stem Cell (OTCBB:ISCO) last month brings the company one step closer to starting human testing of its stem cell technology to treat Parkinson’s disease.
“We have established that the symptoms of Parkinson’s disease can be treated with our stem cell-derived neuronal cells,” Simon Craw, executive vice president, says in an interview with BioTuesdays.com. “No one has successfully done this before.”
While there is human data to suggest that implanting neuronal cells into Parkinson’s disease patients can benefit their symptoms, Dr. Craw says there were two major problems associated with the earlier research. “These cells were sourced from human fetuses, which presents an ethical issue, and fetal neuronal cell transplantation for Parkinson’s caused a movement disorder known as dyskinesia in some patients.”
International Stem Cell’s (ISCO) core technology, parthenogenesis, creates pluripotent human stem cells from unfertilized oocytes (eggs), avoiding the ethical issues associated with the use or destruction of viable human embryos.
ISCO scientists have created the first parthenogenic stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals with minimal immune rejection after transplantation. The company is using its human parthenogenetic stem cells (hpSCs) to treat diseases of the brain, liver and the eye.
“We are the only company in the world with this technology,” Dr. Craw contends, adding that “we have a broad intellectual property portfolio and strong patent protection.”
In the recent ISCO study, researchers used rats and African Green monkeys to test the ability of hpSCs to replace the kind of brain cells destroyed in Parkinson’s and relieve the disease’s movement disorders. The animals were given a neurotoxin to induce Parkinson’s symptoms.
At the American Academy of Neurology last month, ISCO’s researchers reported that treated rats moved more normally, consistent with cell survival and the release of dopamine, a neurotransmitter essential for movement, and that the treated monkeys produced more dopamine, months after treatment. The study also found that many of the injected stem cells remained as neurons and provided a type of neuroprotection in the brain.
Parkinson’s disease is a debilitating neurodegenerative disorder characterized by a progressive degeneration of dopamine-producing neurons in the central nervous system. Current treatments, which replace the lost dopamine, are often useful in the early stages of the disease. But as symptoms grow worse, the efficacy of existing therapies declines, leaving many patients severely disabled.
Ruslan Semechkin, ISCO’s VP of R&D and principal investigator of the study, notes that no adverse events, including dyskinesia, deformations, tumors or overgrowth, were observed in the treatment groups.
“The results are pivotal for our preclinical Parkinson’s program showing, as they do, that the hpSC-derived neuronal cells can potentially ameliorate the behavioral symptoms without triggering dyskinesia,” Dr. Semechkin adds.
In a written statement, Dr. Evan Snyder, co-author of the study and director of the Stem Cells and Regenerative Biology Program at Sanford Burnham Medical Research Institute, says the pilot study represents a “first essential step in bringing cell-based therapies for Parkinson’s disease to clinical trials.”
Dr. Craw says the company has submitted a preclinical plan to the FDA, which outlines additional safety and toxicology studies remaining to be done, and is awaiting a review from the agency. “Our plan is to file an investigational drug application in the first half of 2014 and begin human testing in 2014.”
According to Dr. Craw, there are a number of advantages of the parthenogenesis platform, compared with other stem cell technologies, such as embryonic stem cells, induced pluripotent stem cells and adult stem cells.
“We are most similar to embryonic stem cells except for the fact that our stem cells can be made to be homozygous so that all pairs of chromosomes are identical,” he explains. “This genetic characteristic reduces the ability of the recipient immune system to recognize them as foreign tissue.”
In addition to being ethically superior since no viable embryo is created or destroyed, he points out that hpSCs also offer an important economic benefit in their ability to be expanded and cyro-preserved − something that is not possible with fetal tissue. The company has created a stem cell bank containing 12 hpSC lines, one of which carries the most common immune type and immune-matches approximately 70 million people worldwide, according to Dr. Craw.
Besides Parkinson’s disease, ISCO’s other therapeutic programs include metabolic liver diseases and cornea transplants.
“In our liver program, we have completed a set of rodent studies and have shown safety and efficacy of our hepatocyte-like cells, which are liver cells, generated from our parthenogenic stem cells,” Dr. Craw says. “We are targeting diseases where hepatocyte transplants have been shown to be useful.”
The first liver target in the program is Crigler-Najjar Syndrome Type 1, which is a congenital genetic disorder. It is a rare condition where bilirubin, a substance made by the liver, cannot be broken down. “Our goal here is to use this disease as a proof-of-concept for our hepatocyte-like cells, show clinical benefit in treating the disease and then move out from there, because there are lots of opportunities for our product in a variety of liver diseases,” he contends.
The timelines for Parkinson’s and liver disease are approximately the same, he adds, as the company hopes to file an investigational drug application with the FDA in 2014.
In its cornea program, Dr. Craw says the company has published data showing that it can create corneal tissue from its stem cells. “We’ve already taken our corneal orbs and sutured them on the eyes of human cadavers to examine their mechanical properties. But we need to do more work on optimizing the tissue to show that it is safe before moving into a clinical setting.”
Noting that the market for corneal tissue is mostly in the developing world, where networks of eye banks don’t exist, Dr. Craw says ISCO is collaborating with the Sankara Eye Hospital in Chennai, India to develop its corneal product for the local market. “We are interested in Trachoma, corneal opacity and other conditions affecting the clear part of the front of the eye,” he adds.
To help offset its R&D, the company has established two commercial businesses: Lifeline Cell Technology and Lifeline Skin Care, which together generated sales of $4.6-million in 2012.
Lifeline Cell Technology manufactures and markets high-quality human primary cells, media and reagents. The skin care business manufactures and markets anti-aging topical products based on growth factors and peptides extracted from its human parthenogenetic stem cell platform.
“Longer term, there is a huge potential for licensing our stem cell platform,” Dr. Craw suggests. “If we can prove our platform is useful, companies will want to license either functional cells like hepatocytes or brain cells from us, or take access to the underlying technology and develop therapeutics themselves.”