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新しい研究は、マウスの悪性脳腫瘍を治療する際に、伝統的な漢方薬で使用される天然化合物であるインジルビンに由来する薬の可能性を明らかにしました. に発表されました 細胞レポート医学この研究は、インジルビンの製剤がマウスの生存率をどのように改善し、この薬を人間の参加者による臨床試験に近づけたかを強調しています。 ブラウン大学やハーバード医科大学など、さまざまな機関の科学者がこの研究に協力しました。


科学者たちは、天然化合物であるインジルビンに由来する薬剤が、マウスの悪性脳腫瘍の治療に有望であることを発見しました。 ブラウン大学やハーバード医科大学などの機関との共同研究を含むこの研究は、この薬を人間の臨床試験に近づけます。 6′-ブロモインジルビン アセトキシム (BiA) と呼ばれるこの薬は、腫瘍の成長を遅らせ、生存率を改善し、神経膠芽腫の治療に新しいアプローチを提供します。



Indigo Plants

Indirubin is a natural product present in indigo plants and the active ingredient of the traditional Chinese medicine Dang Gui Long Hui Wan, which is used to treat chronic diseases. Credit: Brown University

In addition to scientists from Brown’s Legorreta Cancer Center and School of Engineering, the team included researchers from the department of neurosurgery at Brigham and Women’s Hospital/Harvard Medical School and Phosphorex, Inc./Cytodigm, Inc.

Glioblastoma is the most common and aggressive type of brain cancer. The standard of care is chemotherapy, radiation and surgery, which may improve symptoms but don’t cure or stop the cancer.

Indirubin is a natural product present in indigo plants and a constituent of the traditional Chinese medicine Dang Gui Long Hui Wan, which has been used in the treatment of chronic myelogenous leukemia, according to the researchers. Derivatives of the indirubin have shown potential for the treatment of cancer through a range of mechanisms. Research published 10 years ago by Lawler and others showed that indirubin slowed the growth of glioblastoma tumors in mice. However, he said, the researchers weren’t able to explain why. What’s more, the modified drug wasn’t very easy to work with, making it challenging for scientists to test dosage levels or efficiently deliver it to the tumor.

As the scientists continued to research the compound, they were contacted by the Massachusetts-based biomedical company Phosphorex, which develops technology to improve pharmaceutical formulations. Phosphorex had patented a formulation of indirubin, called 6’-bromoindirubin acetoxime (BiA), which made the compound easier to use as an injectable cancer treatment.

The researchers tested the nanoparticle formulation of BiA on glioblastoma tumors in mice, focusing on how the drug would affect the immune system. 

Not only did BiA slow the growth and proliferation of tumor cells (confirming the results of previous studies), but it also improved survival via effects on important immunotherapeutic targets.

“The drug impacted the immune system in these mouse experiments in a way that we think could enhance clinical immunotherapy in humans,” explained Lawler, whose lab therapeutic approaches for the treatment of brain cancer.

With a grant from the National Cancer Institute, the researchers will continue to test the drug to see how it interacts with chemotherapy and radiation, with the aim of developing clinical trials for participants with glioblastoma. While scientists have been studying glioblastoma for decades, Lawler said that there haven’t been many significant therapeutic breakthroughs, until now.

“Over the past 20 years or so, there haven’t been many findings of note that have really impacted survival in a meaningful way, so we are very eagerly looking for new approaches,” Lawler said. “This research offers a new approach, and that’s why we’re so excited about it.”

Reference: “PPRX-1701, a nanoparticle formulation of 6′-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models” by Mykola Zdioruk, Jorge-Luis Jimenez-Macias, Michal Oskar Nowicki, Katherine E. Manz, Kurt D. Pennell, Marilin S. Koch, Tomer Finkelberg, Bin Wu, Paul Boucher, Yuji Takeda, Weiyi Li, Raziye Piranlioglu, Alexander L. Ling, E. Antonio Chiocca and Sean E. Lawler, 14 April 2023, Cell Reports Medicine.
DOI: 10.1016/j.xcrm.2023.101019

Additional contributors from Brown included Jorge-Luis Jimenez-Macias, a postdoctoral scholar in Lawler’s lab; Professor of Engineering Kurt Pennell; and Assistant Professor of Engineering Katherine Manz.

The work was supported by the National Cancer Institute (RO1CA166172, R50-CA243706, R21CA259734) and the National Science Foundation (1919870).


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