- An MDA-supported research team has shown in rats that nervous system support cells carrying human mutant SOD1 caused nearby motor neurons to deteriorate and die.
- The findings bolster support for the hypothesis that astrocytes play a key role in motor neuron degeneration in ALS.
An MDA-supported team of scientists has demonstrated in rats that nervous system support cells called astrocytes carrying an SOD1 mutation cause neighboring motor neurons to deteriorate and die.
The finding adds to a growing body of evidence that the star-shaped cells play a key role in the motor neuron degeneration that is the hallmark of ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease). Astrocytes normally support and protect motor neurons.
The team, which included MDA grantee Nicholas Maragakis, reported its findings online Oct. 3, 2011, in Proceedings of the National Academy of Sciences. Read the abstract of the paper, Astrocytes carrying the superoxide disumtase 1 (SOD1 G93A) mutation induce wild-type motor neuron degeneration in vivo.
In a series of studies, the researchers took astrocyte "precursor" cells from the developing spinal cords of research mice carrying a human, ALS-associated SOD1 mutation and injected them into the spinal cords of healthy rats. The cells settled into their new surroundings, developed into astrocytes, and proceeded to cause degeneration and death in surrounding (but not distant) neurons.
The rats also developed signs of motor neuron disease, including weakness in the front legs and respiratory problems.
Only 5 to 10 percent of all ALS cases are familial (inherited), and about 10 to 20 percent of familial ALS cases are caused by mutations in the SOD1 gene. However, the findings could have relevance for sporadic (noninherited) ALS as well. A different study recently showed that astrocytes derived from postmortem tissue taken from people with sporadic ALS were toxic to motor neurons in culture.
The findings should help improve understanding of the disease and pinpoint targets for therapy development.
For more on astrocyte involvement in ALS, see ALS: Not Just About Motor Neurons Anymore.