Dec. 2, 2008

Stem Cells Injected Into Spinal Cord Slow ALS in Rats

Transplantation of immature nervous-system support cells slowed the loss of motor neurons (nerve cells controlling muscle activity) in rats engineered to have a disease resembling human ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease), says a team of researchers from the Johns Hopkins School of Medicine in Baltimore and Invitrogen Corp. in Carlsbad, Calif.

The team published its findings online Oct. 19 in Nature Neuroscience. MDA supported the principal investigator, Nicholas Maragakis at Johns Hopkins, for this work. Jeffrey Rothstein, a longtime MDA grantee and director of MDA's ALS Center at that institution, was also a collaborator on the project.

The investigators injected specialized stem cells known as glial-restricted precursor cells, or GRPs, into the area of the cervical (upper) spinal cord associated with respiratory function, targeting motor neurons responsible for stimulating the diaphragm. (The potential for a therapy to specifically affect diaphragm function is key, as the majority of human patients with ALS ultimately succumb to the disease because of respiratory compromise.)

Approximately one-third of the transplanted cells survived through end-stage disease (when the rats were about 170 days old) and, of those, nearly 90 percent differentiated, or matured, into astrocytes, a type of support cell in the nervous system. No damage to the spinal cord, including cyst or tumor formation, was observed.

The GRPs, the researchers note, remained close to the injection sites, with greater migration along nerve fibers (white matter) than between cell bodies (gray matter).

Rats that received the GRPs lived 16.9 days longer than those that received a placebo. They also showed slower disease progression than the placebo-treated rats did, with longer preservation of respiratory and front-leg function.

Study results suggest the GRPs may have increased clearance of glutamate, a neurotransmitter (signal-transmitting chemical) whose toxic buildup causes overstimulation of the motor neurons and has been implicated as a contributor to ALS. Other therapeutic benefits of the GRPs, investigators note, include a neuroprotective effect caused by the release of neurotrophic factors (proteins responsible for the growth and survival of neurons) and a muted anti-inflammatory response.