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Stem cells on the brain
GAITHERSBURG, Md.—Cytomedix Inc. announced a collaboration last month with Duke University Medical Center for a Phase I clinical study of ALD-451 in brain cancer patients. Cytomedix, which specializes in platelet and adult stem cell technologies, will be responsible for manufacturing ALD-451, and the Duke University Medical Center, through the Robertson Clinical & Translational Cell Therapy Program, will be responsible for funding and all other aspects of the trial.
"We are delighted to be working on this important trial with leading clinicians at Duke University Medical Center, one of the world's leading brain cancer centers for both treatment and research," said Martin P. Rosendale, CEO of Cytomedix, in a statement. "Malignant glioma patients who undergo surgery, radiation therapy and temozolomide treatment oftentimes experience deterioration of neurocognition and have poor patient-reported outcomes. Earlier studies suggest that ALDH bright cells may repair neural brain damage. We expect this study to corroborate those results and look forward to advancing the development of this very promising product candidate."
ALD-451 consists of a population of autologous pluripotent ALDHbr stem cells isolated from a patient's bone marrow by way of Cytomedix's proprietary technology. The adult stem cells express high levels of the enzyme ALDH, an indicator of biological activity in heterogeneous early-stage stem cells, and preclinical research indicates that the cells may help to promote the repair of tissue damage. In an animal model, preliminary data showed that ALDHbr bright cells reduced the severity of intracranial inflammation following brain irradiation, and preclinical research has shown the treatment to garner improvements in motor function, a slowing of brain volume loss, reversal of decline in stroke-induced cell viability and improved blood flow in the brain.
Glial neoplasms represent roughly 40 percent of all primary central nervous system tumors, and approximately 75 percent of them are malignant. Malignant gliomas include World Health Organization (WHO) grade III, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma, and WHO grade IV, glioblastoma and gliosarcoma. Given the invasive nature of the tumors, complete removal is unlikely with surgery, necessitating radiation therapy and chemotherapy, though the former is often associated with a progressive cognitive decline in both children and adults.
The study will enroll up to 12 patients and seeks to demonstrate the feasibility and safety of ALD-451 when administered intravenously to WHO grade IV malignant glioma patients following surgery, radiation therapy and temozolomide treatment. The study will also determine the effects of the treatment on neurocognition, and having secured investigational new drug clearance from the U.S. Food and Drug Administration, is currently open for enrollment.
Dr. Annick Desjardins, the study's principal investigator and an assistant professor of medicine at the Preston Robert Tisch Brain Tumor Center at Duke University Medical Center, says the study will run for about two years. The first year will be set aside for enrollment, after which all patients will be followed for a year to determine the effectiveness of ALD-451 administration.
The study represents the organizations' second trial of late.
"We actually have a very long, established relationship with Duke, part of our intellectual property portfolio was licensed from Duke," says Edward Field, chief operating officer at Cytomedix. "We've done a number of other clinical studies with Duke, including right now an ongoing Phase II study in ischemic stroke. It was actually that study and some of the preclinical work that was done at Duke to support that study that was the origination for the collaboration in the malignant glioma area."
The ischemic stroke study has been going on for about a year now, says Desjardins. Field adds that the study is testing whether a stem cell-based therapy like ALD-451, administered two weeks after a stroke, can enhance neural repair and quality of life.
"We believe that there are a lot of indications that involve complex disorders, complex pathologies, like stroke, where single small-molecule agents focused on a single target are not going to be useful," says Field. "And we think that stem cell therapy with potential multiple mechanisms of action are the only type of therapy that will be able to address some of these complex disorders like stroke."
Desjardins says that industry-academic partnerships such as this are "primordial" for the field.
"I think that it's primordial both for the academic and for the industry to collaborate together and to look for the best treatments for our patients—the collaboration of the knowledge and to be able to bring new therapies for our patients, and for them to have access to it, is something that is absolutely primordial," she says.