Stem cells on the brain

"We are delighted to be working onthis important trial with leading clinicians at Duke UniversityMedical Center, one of the world's leading brain cancer centers forboth treatment and research," said Martin P. Rosendale, CEO ofCytomedix, in a statement. "Malignant glioma patients who undergosurgery, radiation therapy and temozolomide treatment oftentimesexperience deterioration of neurocognition and have poorpatient-reported outcomes. Earlier studies suggest that ALDH brightcells may repair neural brain damage. We expect this study tocorroborate those results and look forward to advancing thedevelopment of this very promising product candidate."

ALD-451 consists of a population ofautologous pluripotent ALDHbr stem cells isolated from a patient'sbone marrow by way of Cytomedix's proprietary technology. The adultstem cells express high levels of the enzyme ALDH, an indicator ofbiological activity in heterogeneous early-stage stem cells, andpreclinical research indicates that the cells may help to promote therepair of tissue damage. In an animal model, preliminary data showedthat ALDHbr bright cells reduced the severity of intracranialinflammation following brain irradiation, and preclinical researchhas shown the treatment to garner improvements in motor function, aslowing of brain volume loss, reversal of decline in stroke-inducedcell viability and improved blood flow in the brain.

Glial neoplasms represent roughly 40percent of all primary central nervous system tumors, andapproximately 75 percent of them are malignant. Malignant gliomasinclude World Health Organization (WHO) grade III, anaplasticastrocytoma, anaplastic oligodendroglioma and anaplasticoligoastrocytoma, and WHO grade IV, glioblastoma and gliosarcoma.Given the invasive nature of the tumors, complete removal is unlikelywith surgery, necessitating radiation therapy and chemotherapy,though the former is often associated with a progressive cognitivedecline in both children and adults.

The study will enroll up to 12 patientsand seeks to demonstrate the feasibility and safety of ALD-451 whenadministered intravenously to WHO grade IV malignant glioma patientsfollowing surgery, radiation therapy and temozolomide treatment. Thestudy will also determine the effects of the treatment onneurocognition, and having secured investigational new drug clearancefrom the U.S. Food and Drug Administration, is currently open forenrollment.

Dr. Annick Desjardins, the study'sprincipal investigator and an assistant professor of medicine at thePreston Robert Tisch Brain Tumor Center at Duke University MedicalCenter, says the study will run for about two years. The first yearwill be set aside for enrollment, after which all patients will befollowed for a year to determine the effectiveness of ALD-451administration.

The study represents the organizations'second trial of late.

"We actually have a very long,established relationship with Duke, part of our intellectual propertyportfolio was licensed from Duke," says Edward Field, chiefoperating officer at Cytomedix. "We've done a number of otherclinical studies with Duke, including right now an ongoing Phase IIstudy in ischemic stroke. It was actually that study and some of thepreclinical work that was done at Duke to support that study that wasthe origination for the collaboration in the malignant glioma area."

The ischemic stroke study has beengoing on for about a year now, says Desjardins. Field adds that thestudy is testing whether a stem cell-based therapy like ALD-451,administered two weeks after a stroke, can enhance neural repair andquality of life.

"We believe that there are a lot ofindications that involve complex disorders, complex pathologies, likestroke, where single small-molecule agents focused on a single targetare not going to be useful," says Field. "And we think that stemcell therapy with potential multiple mechanisms of action are theonly type of therapy that will be able to address some of thesecomplex disorders like stroke."

Desjardins says that industry-academicpartnerships such as this are "primordial" for the field.

"I think that it's primordial bothfor the academic and for the industry to collaborate together and tolook for the best treatments for our patients—the collaboration ofthe knowledge and to be able to bring new therapies for our patients,and for them to have access to it, is something that is absolutelyprimordial," she says.