Hookworms, aggressive, blood-feeding, intestinal nematodes, are currently a leading cause of iron deficiency anemia in the developing world. An inhibitor of platelet aggregation and adhesion has been partially purified and characterized from soluble protein extracts of adult Ancylostoma caninum hookworms. This protein, named the hookworm platelet inhibitor, has an estimated molecular mass of 15 kDa as determined by size-exclusion chromatography. In addition to blocking platelet aggregation in response to a variety of agonists, the partially purified inhibitor also prevents adhesion of resting platelets to immobilized fibrinogen and collagen. Inhibitory monoclonal antibodies were used to identify specific blockade of cell surface integrins GPIIb/IIIa (alphaIIbbeta3) and GPIa/IIa (alpha2beta1), the platelet receptors for fibrinogen and collagen, respectively. This broad-spectrum anti-platelet activity is also present in excretory and secretory products of adult worms, suggesting a biologic role for the hookworm platelet inhibitor in vivo.
Several in vitro and in vivo studies have documented the capacity of gene therapy to favorably modify the biologic functions of intervertebral disc cells with the delivery of the cDNA for various growth factors. Currently, investigators are exploring the efficacy and safety of gene therapy in animal models of degeneration. With promising initial results and an immense potential clinical impact, gene therapy approaches for treatment of intervertebral disc degeneration will continue to receive dedicated research efforts.
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