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Swamping bad cells with good in ALS animal models helps sustain breathing
Date:10/19/2008

tor neurons that spark muscle movement, causing death. The event, called excitotoxicity, also occurs in other neurological diseases.

So on a more basic level, the study adds clout to the principle - in live animals - that excitotoxicity is a major bad guy in ALS and that finding more effective ways to avoid or lessen it could help protect the nervous system.

In their research, the team transplanted some 900,000 glial restricted precursors overall to specific sites in the cervical spinal cord of each model rat in early stages of disease. The GRPs the scientists used began life as what's called astrocyte progenitor cells from healthy rat spinal cord tissue. Following transplant, they transformed into mature, healthy astrocytes, found living alongside sick motor neurons.

Astrocytes are the most common cells in the central nervous system. Work at Johns Hopkins and elsewhere has shown their crucial role in keeping the CNS in healthy balance. Not only are the cells studded with transporter molecules that mop up glutamate; they also maintain proper ion levels and nutrient support of nerve cells.

The study showed that at least a third of the added GRPs "took root" after their transplantation. With time, almost 90 percent of the GRPs had differentiated into astrocytes. Unlike the model rats' own astrocytes, the new ones continued to appear healthy. None of the GRPs damaged the spinal cord or formed tumors - a worry with some stem cell therapies.

Transplanting alternate GRPs - those that the team engineered to lack glutamate transporters - offered none of the protective properties.

"Our findings demonstrate that astrocyte replacement, by transplantation, is both possible and useful," Maragakis explains. "This targeted cell delivery to the cervical spinal cord is a promising strategy to slow that loss of motor neurons in ALS. We hope at some point that these principles will translate to the clinic."

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Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert

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