NEW YORK (Reuters Health) - Polymer conjugation of TNP-470 (fumagillol) -- an angiogenesis inhibitor -- limits the agent’s neurotoxicity and increases its effectiveness, researchers report in the March issue of Nature Medicine.
Some years ago, TNP-470 was shown to inhibit many different tumor types, including human cancers, mouse, rat, hamster and rabbit cancers. In practice, however, there were problems.
As senior investigator Dr. Judah Folkman told Reuters Health, “When TNP-470 first entered clinical trials in the mid-1990s it was an effective anti-cancer drug, but eventually showed neurological side effects, and clinical trials were discontinued. However, now the molecule has been re-engineered so that it has no neurological side-effects and has even higher anti-tumor efficacy.”
Dr. Folkman of Boston Children’s Hospital and colleagues came to these conclusions after a series of studies in mice. Treatment with co-polymer TNP-470 enhanced and prolonged the agent’s action.
Polymer conjugation prevented the drug from crossing the blood-brain barrier and reduced its accumulation in normal organs, thus limiting toxicity. Mice given TNP-470 alone suffered weight loss and neurotoxic effects, but this was not the case in mice given the conjugate.
“This is the first time that an angiogenesis inhibitor has been bound to a polymer in order to target it to endothelial cells in the blood vessels of a tumor,” Dr. Folkman continued. “Based on this paper, this angiogenesis inhibitor can now return to clinical trials.”
Moreover, the study “also paves the way for the development of a novel class of angiogenesis inhibitors which are targeted selectively to the tumor vasculature.”
Source: Nature Med 2004. [ Google search on this article ]
MeSH Headings:Acids, Acyclic: Acrylates: Acrylic Resins: Growth Inhibitors: Neoplasms: Polymethacrylic Acids: Resins, Synthetic: Angiogenesis Inhibitors: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
