Neurologist and neuroscientist Douglas Kerr sees patients every day at the Johns Hopkins University School of Medicine in Baltimore. "I spend about 20 percent of my time," he confides, "attending patients. The rest of my day is in the laboratory, where I focus on spinal cord inflammation disorders, clinically as well as in research."

Kerr spells motor neuron disease "ALS" - amyotrophic lateral sclerosis - better known as Lou Gehrig's disease. ALS afflicts about 350,000 patients worldwide, 30,000 of them in the U.S. Half of those U.S. patients are dead of their disease within three years of diagnosis - around 40 or older. It usually begins in the prime of life with the loss of function in hands, forearms, shoulders and feet, followed by progressive muscular weakness and wasting, muscle twitching, and wasting of muscles in chewing, swallowing and breathing - leading to inevitable death.

Kerr is first author of a paper in the Journal of Neuroscience, released online June 27, 2003. Its title: "Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injury."

"Our finding in this article," Kerr observed, "is essentially designing and testing a faithful animal model of human ALS, which has many similarities but is not identical to ALS, motivated by our research. I'm intrigued by its relationship to potential therapies of the motor neuron diseases.

"If you look at the cell body of a motor neuron," Kerr explained, "by a staining that identifies nerve terminals, there are somewhere like 30 or so little punctate synapses on that motor neuron's cell body - all feeding that neuron information of various types. Some of those synapses are from descending motor neurons that originated in the brain."

Synapses Shorted In Neurodegeneration

"When an injury occurs - and this happens in a whole series of neurodegenerative diseases - you now see the same staining. And even if that motor neuron is still there, it has no synaptic contacts, so it's completely dumb. So when you transplant the cells, it's to facilitate their reafferentation - meaning the synapses reform, reconnect. A general response to any injury is that the connections on an at-risk cell will peel back, like rats leaving a sinking ship. They sense the destruction of neurons and pull away.

"The significance of this finding," Kerr told BioWorld Today, "is that stem cells may work in restoring function, and that ability may be independent of rewiring the nervous system. That would be a tall order. If by contrast we view this as the low-hanging fruit, that will be the easier task in supporting and accentuating the function of the host cells."

For starters in devising their model of motor neuron injury, Kerr and his co-authors treated their stable of rats to a dose of Sindbis virus. This moderate mosquito-borne pathogen causes febrile illness in Africa, Australia and other countries. "It's a model that is reproducible and rapidly stimulates the onset of a neurodegenerative process," Kerr explained. "And it's opposed to the SOD [superoxide dismutase] mutant ALS model, which takes 130 days. SOD1 is a widely used genetic model of ALS, although a bit cumbersome. With Sindbis, we generated the model, and stimulated the neurodegenerative process within a week," he recounted. The hind limbs were preferentially affected - as they are in ALS.

"About 10 days after the virus is no longer a participant within this disease process," Kerr went on, "because it is cleared by the virus itself; instead, the process that has been set in motion continues - and that's the neurodegenerative course characterized by motor neuron death.

"We don't know the answer to when and why motor neuron death occurs," Kerr allowed, "although much of my research effort is focused on understanding that. And the truth is that the virus triggers an excitotoxic death of motor neurons. It's separable from viral infection, but the virus triggers this pathway to cytotoxic death. Ten days after the viral infection, by which time the virus is cleared, leaving behind the hind-limb lesions, we put a cannula - a catheter - into the base of the rats' spines, which empty into the spinal fluid surrounding the spinal cord. Next we administered the stem cells through the cannula."

Stem Cells Winners In Blinded Rat Trial

"The animals then received a series of treatments," Kerr related. "These ranged from the human stem cells, or killed stem cells, or human nonstem cells, or just dummy surgical treatment, to surgical treatment plus saline. All of those interventions represent groups of animals, and all the animals were then coded so that we became blinded as to which animal was within which group. Animals were scored, but we didn't know for the next six months which one was which - to which group that rat belonged.

"It wasn't until six months later that we actually broke the code," Kerr went on, "but in three months we started to see some animals recovering; they kind of moved their hind limbs back under them a bit. They couldn't really bear weight but could budge a little. We didn't know which group they were in. At six months those animals had continued to further recover and at that point we broke the code. We then found out that every single one of the animals that had recovered was in the stem cell-transplanted group. The animals did somewhat better. There was some recovery. It wasn't complete but they certainly recovered. So we were elated to see that there was a correlation between the two.

"Transforming growth factor [TGF-a] and brain-derived neurotrophic factor [BDNF] have been around for about 10 years," Kerr recalled. "BDNF is noted for enhancing axonal growth, while TGF-a protects from cell death and supports motor neuron survival."