Defining ALS
Time and Place
It’s hard to believe that the pathology of ALS—exactly what happens when and where in the disease—has never been fully described. But that information, say Carol Milligan and Ron Oppenheim (Wake Forest U. School of Med., Winston-Salem, NC), would lay an invaluable foundation for therapy. Milligan suspects that “one reason clinical trials have been unsuccessful may be because treatments target steps that occur too far down in the cascade leading to motor neuron death.” Identifying the earliest events may change that. The researchers have spent nearly two years cataloguing the changes in nerve and muscle cell biology in the SOD1 mouse model of ALS from the animal’s early days. Already, they’ve verified that pathology begins nearly two months before symptoms appear. Their findings strengthen reports of many Packard colleagues, confirming they’re on the right track, saving countless hours. Downhill for Mitochondria
Giovanni Manfredi (left) and Jordi Magrané (both, Cornell University) continue to report the changes in the cell’s powerhouses—its mitochondria—that come with ALS, with the idea that destroying the cell’s ability to supply energy is a sure recipe for death and a key process to reverse in therapy. They’ve moved from finding abnormal mitochondria—in shape, number and behavior—in neurons from ALS model animals to finding mitochondrial changes in the animals themselves. The damage is most obvious at the synapses, the crucial site of early injury in ALS. | 
