Therapeutic Approaches

The finding that marrow stromal cells (MSCs) infused into irradiated transgenic mice with OI were engrafted in bones and contributed to the formation of osteoblasts led to a trial of bone marrow transplantation in children with type III OI.[13] The trabecular bone histological examination showed changes indicative of new dense bone formation; increase in bone mineral content and reduction in the frequency of fractures were also reported. The goal of gene therapy of dominant negative disorders such as OI must be to shut off the expression of the mutant allele, creating a functionally null allele. Selective suppression of the expression of the mutant allele in connective tissues could modulate the clinically severe forms of OI into the biochemical equivalent of mild type I OI. The specificity of mutant allele suppression observed in the experiments with the use of antisense oligonucleotides appears to be insufficient for therapeutic trials. The use of ribozymes is an alternative and particularly attractive approach of antisense therapy.[14] The specificity of their action is greatly improved because they can cut only RNA molecules containing the specific cleavage site. For OI, about 25% of the causative type I collagen point mutations generates a novel ribozyme cleavage site. Information on the required level of suppression can be obtained from studies of mutant type I collagen expression levels in bones of clinically mild mosaics. The use of MSCs as vehicles to deliver therapeutic genes to bones is being evaluated in laboratory and animal studies. In this approach, bone marrow is harvested and, ex vivo, mesen-chymal stromal cells are isolated, expanded in numbers,

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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