(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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