A new analyze has revealed the prospective of a drug derived from indirubin, a pure compound made use of in regular Chinese medicine, in treating malignant mind tumors in mice. Posted in Cell Stories Medicine, the exploration highlights how a formulation of indirubin improved mice’s survival charges and moved the drug nearer to medical trials with human participants. Experts from various establishments, like Brown University and Harvard Professional medical Faculty, collaborated on the examine.
Researchers found that a by-product of the organic compound indirubin presents a new approach to dealing with glioblastoma in mice, which will inform foreseeable future exploration in human beings.
Researchers have uncovered that a drug derived from the organic compound indirubin exhibits assure in managing malignant mind tumors in mice. The examine, involving collaboration involving institutions like Brown College and Harvard Medical School, delivers the drug nearer to human medical trials. The drug, identified as 6’-bromoindirubin acetoxime (BiA), slowed tumor expansion and enhanced survival fees, providing a new technique for glioblastoma therapy.
A new analyze demonstrates how a drug made from a all-natural compound used in conventional Chinese medicine will work against malignant mind tumors in mice, developing a promising avenue of investigation for glioblastoma treatment method.
In the review, released on April 14 in the journal Cell Reports Medicine, researchers showed how a formulation of the compound, called indirubin, improved the survival of mice with malignant brain tumors. They also tested a new formulation that was easier to administer, taking the potential pharmaceutical approach one step closer to clinical trials with human participants.
“The interesting thing about this drug is that it targets a number of important hallmarks of the disease,” said Sean Lawler, lead author, associate professor of pathology and laboratory medicine, and researcher at the Legorreta Cancer Center of Brown University. “That’s appealing because this type of cancer keeps finding ways around individual mechanisms of attack. So if we use multiple mechanisms of attack at once, perhaps that will be more successful.”
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).
