The Effect of Insulin-binding Serum Globulin on Insulin Requirement

Prout, Thaddeus E.; Katims, Robert B.

doi:10.2337/diab.8.6.425

Cited by 17 publications

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“…We conclude that the development of antibodies does not necessarily lead to increased clearance or inactivation of the biological effect of the protein. Our data are consistent with the fact that a large fraction of patients that are treated with porcine insulin (65)(66)(67)(68), growth hormone (69), factor VIII (70), or glucocerebrosidase (71, 72) develop antibodies, and the majority of these antibodies do not have an adverse effect upon the biological response to the protein. Indeed, most patients that were treated with porcine insulin developed antibodies that prolonged the half-life of radiolabeled insulin in vivo without blocking its effects upon glucose metabolism (65)(66)(67)(68).…”

Section: Discussionsupporting

confidence: 87%

“…Our data are consistent with the fact that a large fraction of patients that are treated with porcine insulin (65)(66)(67)(68), growth hormone (69), factor VIII (70), or glucocerebrosidase (71, 72) develop antibodies, and the majority of these antibodies do not have an adverse effect upon the biological response to the protein. Indeed, most patients that were treated with porcine insulin developed antibodies that prolonged the half-life of radiolabeled insulin in vivo without blocking its effects upon glucose metabolism (65)(66)(67)(68). Although antibodies that block the effect of a protein can pose a serious clinical problem for the treatment of diabetes, growth hormone deficiency, hemophilia, or Gaucher disease (65-70; 73), we conclude that not all antibodies are deleterious.…”

Section: Discussionsupporting

confidence: 87%

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Therapeutic levels of human protein C in rats after retroviral vector-mediated hepatic gene therapy.

et al. 1998

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Protein C deficiency results in a thrombotic disorder that might be treated by expressing a normal human protein C (hPC) gene in patients. An amphotropic retroviral vector with a liver-specific promoter and the hPC cDNA was delivered to rat hepatocytes in vivo during liver regeneration. Expression of hPC varied from 55 to 203 ng/ml (1.3-5.0% of normal) for 2 wk after transduction. Expression increased to an average of 900 ng/ml (22% of normal) in some rats and was maintained at stable levels for 1 yr. All of these rats developed anti-hPC antibodies and exhibited a prolonged hPC half-life in vivo. The hPC was functional as determined by a chromogenic substrate assay after immunoprecipitation. We conclude that most rats achieved hPC levels that would prevent purpura fulminans, and that hepatic gene therapy might become a viable treatment for patients with severe homozygous hPC deficiency. Anti-hPC antibodies increased the hPC half-life and plasma levels in some rats, but did not interfere with its functional activity. Thus, the development of antibodies against a plasma protein does not necessarily abrogate its biological effect in gene therapy experiments.

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