Endocrine Abstracts

Background: Acromegaly is associated with increased morbidity and mortality, however currect medical treatment controls the disease in <60% of patients. Pegvisomant, a pegylated GH antagonist, controls the disease in over 95% of cases, but is not cost effective as it requires high dose daily injections and has side-effects. We have developed a technology for generating a long acting potent GH antagonist.Hypothesis: That a GH antagonist fused to GH bi...

Background: The development of recombinant biologics has had a major impact on many diseases. However, most biologics are rapidly cleared from the body and therefore require frequent injection regimens. There is therefore a need for technologies that allow the half-lives of these molecules to be extended in a predictable manner.HypothesisIncreasing numbers of N-linked glycosylation motifs between two GH molecules leads to gradually...

Background: The development of recombinant biologics such as interferon, insulin and Growth Hormone (GH) has had a major impact on the management of diseases including hepatitis, diabetes and GH-deficiency. However, most biologics undergo rapid renal filtration and proteolytic degradation, necessitating frequent dosing regimens. Pegylation can successfully delay clearance but has several drawbacks including potential toxicity, expense and reduced activity. There is therefore n...

Background: Leptin has multiple functions including modulating energy homeostasis and the immune response. Leptin is an important target for therapy to modulate the immune response in several autoimmune diseases. Although the structure of leptin is known, that of its receptor remains unsolved. The aim of this project was to express and purify the extracellular domain the leptin receptor (ObR) in order to carry out functional and crystallisation studies to elucidate the mechani...