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The goal of this proposal has been to determine whether a novel nanovector consisting of hydrophilic carbon clusters (HCCs) (pegylated) can serve as a therapeutic in a murine model of amyotrophic lateral sclerosis. HCCs were produced by Dr. James Tour of Rice University and provided to Dr. Grill to assess in his colony of G93A hSOD1 mutant mice. Aims were to determine whether PEG-HCCs functionalized with antibodies against the transferrin receptor could enhance lifespan, protect motoneurons and enhance motor function when delivered via sustained intravenous route at the first sign of disease. Second aim was to assess whether riluzole, in combination with functionalized PEG-HCCs could enhance the outcomes used in Aim 1. Progress in this grant was significantly reduced through two incidences with the Jackson Laboratory who had improperly sent us the wrong animals for the study. This resulted in a significant loss of time on two occasions as the colony needed to be refurbished. We report now, however that PEG-HCCs produce a significant enhancement in several indices of motor function, but not enhanced lifespan, when applied to the G93A mouse., The original document contains color images.

Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disorder characterised by selective loss of motor neurons with accompanying muscle paralysis and respiratory failure. Despite progressive paralysis in trunk and extremity muscles, disturbed eye motility is not a hallmark of ALS. Extraocular muscles (EOMs) of terminal ALS patients show far less morphological signs of disease than their limb muscles. One of the earliest signs of the disease in the transgenic G93A SOD1 mouse model of ALS is loss of motor neuron contact at the neuromuscular junctions (NMJ) in limb muscles. We used immunohistochemistry to identify NMJs and evaluate innervation in EOMs and limb muscles of G93A mice. In G93A limb muscles, loss of axonal contact was seen in 6-82 percent of the NMJs. On the contrary, the degree of endplate occupancy in the EOMs did not differ between transgenic mice and wild-type controls. We propose that EOM-specific properties make these muscles more resistant to the underlying pathophysiological process of ALS and that the EOMs are a useful model to advance our understanding of ALS.