The Project ALS research advisory board voted unanimously in January to re-up the four-lab consortium working to understand why the motor neurons controlling the eyes—ocular motor neurons, or OMNs—remain functional in ALS even as motor neurons enervating the limbs are destroyed. In its first quarterly meeting of 2016, held last Friday, March 18, researchers from member labs shared progress toward conferring OMNs' resistance on vulnerable motor neuron populations. The Project ALS consortium model means that each of these individual studies informs and supports efforts in other participating labs, and regular meetings like last week's give collaborators the chance to share their newest data, as follows:
—Scientists in the lab of Elizabeth Engle (Harvard), consortium director, have identified and characterized a small group of genes that are expressed differently in OMNs. Now they are conducting careful analysis of each of these to determine which gene(s) might be the key to ocular motor neuron resistance in ALS.
—John Smerdon, a PhD student in the lab of Hynek Wichterle (Columbia), has discovered important differences in the electrophysiology of motor neurons with ALS. Notably, preliminary results from his tests on ALS OMNs suggest that they resemble healthy motor neurons.
—Esteban Mazzoni (New York University) and colleagues in his lab are testing how OMNs and limb-enervating motor neurons respond differently to ALS-like stressors, and to different ALS models, to determine which components of the disease process set OMNs apart.
—Experts in creating highly specified motor neuron subtypes in Parkinson’s disease, the lab of Lorenz Studer (Memorial Sloan Kettering) is now bringing its skills to bear on OMN creation.
—A post-doctoral fellow in the lab of former collaborator Chris Henderson (Columbia, Biogen) is undertaking a detailed study of motor neurons that control facial movements. Given their position, a better understanding of these overlooked cells will provide important clues into understanding motor neuron subtypes.
Given the complexity of motor neuron genetics, circuitry, electrophysiology, and anatomy, the Project ALS strategy is to attack this question of selective vulnerability—which we believe is at the heart of understanding motor neuron death in ALS—from all angles. Our goal in the second phase of this consortium, even as we work to better understand why some motor neurons resist the disease while others are destroyed, is to apply what we’ve learned so far toward therapeutic targets that may slow or stop ALS.