Stem Cell Neurogenesis
“We work mainly in the field of growth factors, not transplants,” says Markus Jerling, Ph.D., CMO, NeuroNova. “We were previously taught that we could not regenerate cells in the central nervous system, but new research has shown that’s not true. We have screened a number of compounds to stimulate neuronal growth and regeneration.”
Dr. Jerling will be presenting on two projects: the first looks at a proposed treatment for Parkinson’s disease wherein platelet-derived growth factor, a protein that promotes neuronal stem cell proliferation, is infused with a pump directly into a fluid filled cavity in the brain. He points out that NeuroNova is working closely with Medtronic, which supplies the implantable pumps and catheters.
“What has been administered locally in the brain can stimulate brain cells in this area,” remarks Dr. Jerling. “Our next step is to show results in typically affected Parkinson’s patients. We have good animal models—we’ve administered this in monkeys and demonstrated by PET imaging increased dopamine turnover and symptom relief patterns. Treatment is short, approximately two weeks, but the effects are long-lasting. By kick-starting the process, it will continue on its own.”
Dr. Jerling says his group suspects that further treatment periods may be necessary, but the option to retreat in a similar fashion is open.
“Currently, the study proposal is under regulatory review, and we expect to start in patients with relatively advanced Parkinson’s,” states Dr. Jerling. “So part of my talk will also cover some of the methods for assessing disease activity and designing such a trial in man.”
An advantage of stem cell stimulation using an implanted pump is that dosing can be stopped or modified, in contrast to stem cell transplantation where cells become independent. Similar approaches have been tested previously, but technologies have advanced considerably in the last ten years.
Dr. Jerling will also discuss a similar project that involves the delivery of the growth factor VEGF to ALS patients. “The catheter will be in the same place, but it will be continuous treatment—24/7. The ALS disease mechanism is not well known, and it affects a wider area of the brain. ALS patients have less of a capacity to increase VEGF production when needed, and our aim is for all patients with a diagnosis to get treatment.”
But such an undertaking requires multiple regulatory approvals—not only for the drug, but also for the device delivering the drug and the ethics. Dr. Jerling notes that some approvals have come in, and suspects the approval process will be complete by late 2008. “For ALS the medical need is extremely high,” Dr. Jerling adds. “Currently, there is no effective treatment—the only approved drug adds 2–3 months to a patient’s life.”
And the applications are broad. “We’ve selected two diseases for study, but the approach, as such, is of potential benefit for any neurodegenerative disease,” concludes Dr. Jerling.
Dr. Deans will be addressing isolation and clinical expansion of adult adherent bone marrow stem cells as well as preclinical safety and efficacy models for stem cell treatment of ischemic heart and brain injury. “Probably half the talk will deal with where we stand in clinical development,” he explains.
Athersys has been able to file with the FDA and open two clinical trials for treatment of acute myocardial infarct and limiting morbidity from graft versus host disease in allogeneic HSC transplant. Dr. Deans reports that the firm hopes to file an IND later this year for treatment of stroke.
“We covered quite a bit of ground in eight months,” he remarks. “The regulatory environment of the FDA has been supportive of adaptive clinical trials that have allowed us to test more indications in parallel. Once you are down this path you can use the same undifferentiated cell product to bring several indications forward. We’ve made significant advances, and we can leverage the safety profile proven at early stages.”
Dr. Deans also notes that Athersys has emphasized safety testing in immunodeficient animals, as well as applying new technologies looking at changes in gene-methylation patterns by microarrays, or chromosomal integrity by CGH.
“The cell has the potency and safety profile that’s required. Researchers are trying to show the safety of cell products, and it’s a significant plateau to reach. This allows for more progress in the cell therapy space, a good sign for the industry.”
There are competitive and collaborative opportunities in this space, Dr. Deans notes. “The opportunity is large, since these are coalescing technologies.” He added that he sees two primary business models: Single-channel dose from donor to patient, a personalized medicine approach that has not been a good business model.
“The other approach is a universal product from a single donor—unlimited and undifferentiated cells. This is the way the industry is headed,” he continues. “There is new attention paid to personalized medicine with the advent of IPS (pluripotent stem cells from an individual that can produce cells for a personalized medicine approach). However, this shifts the model to a banking and service-based business, which hasn’t been attractive for investors or pharma.”