Post-polio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study.

Post-polio syndrome (PPS) is characterized by new muscle weakness, atrophy, fatigue and pain developing several years after the acute polio. Some studies suggest an ongoing inflammation in the spinal cord in these patients. From this perspective, intravenous immunoglobulin (IvIg) could be a therapeutic option. We performed a double-blinded randomized controlled pilot study with 20 patients to investigate the possible clinical effects of IvIg in PPS. Twenty patients were randomized to either IvIg 2 g/kg body weight or placebo. Primary endpoints were changes in pain, fatigue and muscle strength 3 months after treatment. Surrogate endpoints were changes in cerebrospinal fluid (CSF) cytokine levels. Secondary endpoints were pain, fatigue and isometric muscle strength after 6 months. Patients receiving IvIg reported a significant improvement in pain during the first 3 months, but no change was noted for subjective fatigue and muscle strength. CSF levels of tumour necrosis factor-alpha (TNF-alpha) were increased compared with patients with non-inflammatory neurological disorders. In conclusion, in this small pilot study no effect was seen with IvIg treatment on muscle strength and fatigue, however IvIg treated PPS patients reported significantly less pain 3 months after treatment. TNF-alpha was increased in the CSF from PPS patients. The results are promising, but not conclusive because of the low number of patients studied.

Sec6 is localized to the plasma membrane of mature synaptic terminals and is transported with secretogranin II-containing vesicles.

The sec6/8 (exocyst) complex is implicated in targeting of vesicles for regulated exocytosis in various cell types and is believed to play a role in synaptogenesis and brain development. We show that the subunits sec6 and sec8 are present at significant levels in neurons of adult rat brain, and that immunoreactivity for the two subunits has a differential subcellular distribution. We show that in developing as well as mature neurons sec6 is concentrated at the inside of the presynaptic plasma membrane, while sec8 immunoreactivity shows a diffuse cytoplasmic distribution. Among established, strongly synaptophysin-positive neuronal boutons, sec6 displays highly differential concentrations, indicating a role for the complex independent of the ongoing synaptic-vesicle release activity. Sec6 is transported along neurites on secretogranin II-positive vesicles, while sec6-negative/secretogranin II-positive vesicles stay in the cell body. In PC12 cells, sec6-positive vesicles accumulate at the plasma membrane at sites of cell-cell contact. Neuronal induction of the PC12 cells with nerve growth factor shows that sec8 is not freely soluble, but may probably interact with cytoskeletal elements. The complex may facilitate the targeting of membrane material to presynaptic sites and may possibly shuttle vesicles from the cytoskeletal transport machinery to presynaptic membrane sites. Thus, we suggest that the exocyst complex serves to modulate exocytotic activity, by targeting membrane material to its presynaptic destination.

The cellular and developmental expression of hrs-2 in rat.

The molecular events underlying vesicular trafficking probably involve the formation and dissolution of protein complexes between integral components of the vesicle and its target membrane. SNAP-25 is associated with the plasma membrane and is a component of a core protein complex thought to be essential for neurotransmitter release. We have previously characterized a protein, hrs-2, that interacts with SNAP-25 and inhibits secretion from permeabilized PC12 cells. The cellular localization and developmental expression patterns of a number of proteins involved in the secretion machinery have been documented. To understand more about the possible cellular role of hrs-2, we have examined hrs-2 distribution, developmental expression and subcellular localization in rat tissues and cell lines. We show herein that the distribution of hrs-2 in brain and periphery parallels that of SNAP-23/25, and that recombinant hrs-2 binds to both SNAP-23 and SNAP-25. Hrs-2 mRNA and protein are found almost ubiquitously in neurons in the brain. Hrs-2 mRNA is expressed in the neural tube at E10 and thereafter mRNA and protein levels remain relatively constant in the whole brain through adulthood. In cultured PC12 cells, endogenous hrs-2 is expressed in the cytoplasm and on the limiting membranes of multivesicular bodies. Overexpression of hrs-2 in mammalian cells results in the appearance of large intracellular compartments that are labelled with hrs-2 antibodies. The wide distribution, the interaction with SNAP-23 and the localization on multivesicular body membranes suggest a general role for hrs-2 in cellular machinery.