X-Message-Number: 14617
Date: Wed, 4 Oct 2000 15:57:47 -0700 (PDT)
From: Doug Skrecky <>
Subject: long term correction of obesity and diabetes

(rather amazing when you think of it)

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Title
  Long-term correction of
  obesity and diabetes in genetically obese mice by a single intramuscular
  injection of recombinant adeno-associated virus encoding mouse leptin.
Source
  Proceedings of the National Academy of Sciences of the United States of
  America.  94(25):13921-6, 1997 Dec 9.
Abstract
  The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype
  that includes obesity and non-insulin-dependent diabetes mellitus. This
  phenotype closely resembles the morbid obesity seen in humans. In this study,
  we demonstrate that a single intramuscular injection of a recombinant
  adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in
  ob/ob mice leads to prevention of obesity and diabetes. The treated animals
  show normalization of metabolic abnormalities including hyperglycemia,
  insulin resistance, impaired glucose tolerance, and lethargy. The effects of
  a single injection have lasted through the 6-month course of the study. At
  all time points measured the circulating levels of leptin in the serum were
  similar to age-matched control C57 mice. These results demonstrate that
  maintenance of normal levels of leptin (2-5 ng/ml) in the circulation can
  prevent both the onset of obesity and associated non-insulin-dependent
  diabetes. Thus a single injection of a rAAV vector expressing a therapeutic
  gene can lead to complete and long-term
  correction of a genetic disorder. Our study demonstrates the
  long-term correction of a
  disease caused by a genetic defect and proves the feasibility of using
  rAAV-based vectors for the treatment of chronic disorders like obesity.

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