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Drug Derived From Chinese Medicine Improves Brain Tumor Survival in Mice
author:Sarah Whelansource:Technology Networks 2023-04-18 [Medicine]
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A new study has suggested that a drug formulation derived from indirubin, a molecule found in indigo plants used in Chinese medicine, can improve glioblastoma survival in mice. The research is published in Cell Reports Medicine.

 

Poor prognoses with glioblastoma

Glioblastoma is one of the most common types of brain cancer. It is very aggressive, with less than 5% of patients surviving 5 years after their diagnosis. The current standard treatment includes a combination of chemotherapy, radiation and surgery – however, this only improves the symptoms of this incurable disease.

 

Despite incremental improvements in therapies, the odds of long-term survival with glioblastoma remain slim, and further advancements in therapies are needed. One possible prospect is indirubin, a natural compound in indigo plants used to produce some traditional Chinese medicines. Previous studies have suggested that indirubin derivatives may have “anti-inflammatory, anti-tumor and neuroprotective effects,” the researchers write.

 

2011 study by the current researchers suggested that an indirubin derivative, 6’-bromoindirubin acetoxime (BiA), slowed the growth of glioblastoma tumors in mouse models. However, they were unable to determine how or why. Additionally, the indirubin derivative used in the study was challenging to use in terms of assessing dosages and delivering to the tumor.

 

Testing a new formulation

Biomedical company Phosphorex contacted the researchers to investigate their patented BiA formulation, PPRX-1701, which is more suited for use as an injectable treatment.

 

Experiments with mouse models showed that BiA slowed the growth and proliferation of glioblastoma cells, confirming the findings from their previous study. In one model, three doses of PPRX-1701 per week for two weeks significantly increased median survival to 42 days compared to 30 days for the placebo group.

 

Additionally, the researchers observed that BiA also improved survival by influencing important pathways also targeted by immunotherapies.

 

“The drug impacted the immune system in these mouse experiments in a way that we think could enhance clinical immunotherapy in humans,” said Professor Sean Lawler, senior author of the study and associate professor of pathology and laboratory medicine at Brown University.

 

“The interesting thing about this drug is that it targets a number of important hallmarks of the disease,” Lawler added. “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.”

Additional preclinical studies needed

The researchers expand on some limitations of the study, stating that the mouse models used “are not genetically typical of GBM”, and that only female mice were used. Therefore, further studies using other, more typical mouse models of glioblastoma are required to support these preclinical findings.

 

“However, together with the presented models in this study, this approach will be an important part of the complete preclinical validation prior to further steps toward testing PPRX-1701 in clinical trials,” the researchers write.

 

Reference: Zdioruk M, Jimenez-Macias JL, Nowicki MO, et al. PPRX-1701, a nanoparticle formulation of 6′-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models. CR Med. 2023. doi: 10.1016/j.xcrm.2023.101019