Research press release


Nature Biomedical Engineering

Non-antigenic stealth drug for treating diabetes



Ashutosh Chilkotiたちは、2型糖尿病の治療に用いられる薬物(エキセンディン-4)に、エチレングリコールの短いセグメントを有するポリマー(それによって柔軟な桿状の分子ブラシのような姿をしている)を付加させると、患者由来の抗PEG抗体に対する修飾薬の反応性が消失することを明らかにした。このポリマー修飾薬はエキセンディン-4の血中循環時間を延長させ、単回注射によるマウスの正常血糖値持続時間が、薬物単体ではわずか6時間であったのに対し、最長5日間(120時間)に達することも分かった。著者たちは、その薬物修飾法が治療薬の安全性および有効性を向上させるための次世代技術となることを示唆している。

A method for extending the duration of the therapeutic effect of a type 2 diabetes drug in mice and that, crucially, eliminates a common adverse effect to drugs associated with pre-existing antibodies in patients, is described in a paper published online this week in the new journal Nature Biomedical Engineering.

Modifying a drug with an inert, biocompatible polymer such as poly(ethylene glycol) - a flexible chain-like molecule, also known as PEG - can reduce the drug’s interaction with the immune system. However, chronic exposure to PEG, which is present in commonly used consumer products, leads the immune system to generate antibodies against it, reducing the clinical efficacy of PEG-modified drugs and increasing the risk of adverse reactions to them.

Ashutosh Chilkoti and colleagues show that appending a polymer bearing short segments of ethylene glycol (and thus resembling a flexible, rod-shaped molecular brush) to a drug (exendin-4) used to treat type 2 diabetes eliminates the reactivity of the modified drug towards patient-derived antibodies against PEG. They also show that the polymer-modified drug increases the drug’s circulation time in blood, with a single injection maintaining normal blood glucose levels in mice for up to five days (120 hours), compared with only 6 hours for the drug alone. The authors suggest that their drug-modification strategy constitutes a next-generation technology for improving the safety and efficacy of therapeutics.

doi: 10.1038/s41551-016-0002


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