Cisbio eBook - 24

Trends in Protein-Protein Interactions Research | Advantages May Place Peptides Ahead of Small-Molecule Drugs


The peptide can be delivered subcutaneously and it crosses the blood-
brain barrier. "While an oral drug is always easier to administer," notes
Dr. Dewji, "subcutaneous administration is still a relatively easy route of
administration compared to intravenous delivery."

Modulating Metabolism
"Our story began when we observed what was happening in the clinic
with patients undergoing bariatric surgery, and then we went to the
preclinical stage to select our molecule, and from there we went back
into the clinic," recalls Cristina M. Rondinone, Ph.D., vice president of
research and development and head of cardiovascular, renal, and metabolic diseases at MedImmune.
A key research effort at MedImmune is focusing on peptide therapeutics
to treat diabetes and obesity. While existing therapeutic options may be
helpful, none of them are curative. A critical observation was that the
glucose metabolism improvements that occur after bariatric surgery
precede the weight loss seen in patients.

Glucagon-like peptide 1 (GLP1, 7-36) molecule. GLP-1 analogues are used in the treatment of
diabetes and include exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide.
Stylized combination of a semi-transparent surface model with a cartoon representation.
Gradient colouring (N-terminus blue, C-terminus pink).

24 |

"This indicates not only that something happened very fast, but also that
the mechanisms for improving glycemic control are different from the
ones to reduce body weight," maintains Dr. Rondinone. As a consequence
of bariatric surgery, the duodenum is bypassed, and there is a change
in the secretion of peptides, hormones, and other biologically active
molecules by the intestine. "We were interested in investigating which of

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