The high cost of spasticity in multiple sclerosis to individuals and society.

BACKGROUND: Spasticity is an extremely common, distressing and disabling symptom of multiple sclerosis. Limited data suggest the associated health care costs correlate with increasing severity and place a high economic burden on individuals, health care systems and society. OBJECTIVE: The aim of this study was to quantify the impact of multiple sclerosis spasticity on health care resources and the associated costs at different levels of severity in people with multiple sclerosis in the United Kingdom. METHODS: An online survey was carried out to understand the resources used in the management of spasticity in multiple sclerosis. The questionnaire asked health care specialists to estimate their involvement and the resource use associated with different levels of spasticity, and the survey outputs were used to derive the resource costs. RESULTS: The level and cost of care substantially increased with the degree of spasticity. Key factors contributing to high annual costs per patient were home care, hospital admissions and high-cost items, such as hospital beds. CONCLUSIONS: Based on the survey results, it can be assumed that managing spasticity early and effectively could result in substantial cost savings, in addition to the improvements in health-related quality of life.

HPC3 is a new human polycomb orthologue that interacts and associates with RING1 and Bmi1 and has transcriptional repression properties.

Polycomb group (PcG) proteins were first described in Drosophila as factors responsible for maintaining the transcriptionally repressed state of Hox/homeotic genes in a stable and heritable manner throughout development. A growing number of vertebrate genes related to the Drosophila PcG proteins have recently been identified, including two Polycomb orthologues, Pc2 and M33. PcG proteins form multiprotein complexes, termed PcG bodies, that are thought to repress transcription by altering chromatin structure. Here we report the identification and characterization of HPC3 (human Polycomb 3), a novel PcG protein isolated in a yeast two-hybrid screen using human RING1 as bait. HPC3 shows strong sequence similarity to Drosophila Pc and also to vertebrate Pc2 and M33, particularly within the chromodomain and C-box. Previous studies indicate that M33 and human Pc2 (HPC2) can interact with RING1, and we show here that HPC3 also binds to RING1. This interaction is dependent upon the HPC3 C-box but, only partially on the RING finger of RING1. In contrast to HPC2, HPC3 interactions with RING1 are only observed in vivo with covalently modified forms of RING1. HPC3 also colocalizes with other PcG proteins in human PcG bodies. Consistent with its role as a PcG member, HPC3 is able to act as a long range transcriptional silencer when targeted to a reporter gene by a heterologous DNA-binding domain. Taken together, these data suggest that HPC3 is part of a large multiprotein complex that also contains other PcG proteins and is involved in repression of transcriptional activity.