Study of the Week: A Method for Crossing the Blood-Brain Barrier to Treat Glioblastoma

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.


This week’s study is…

A Pt(IV)-conjugated brain penetrant macrocyclic peptide shows pre-clinical efficacy in glioblastoma

We previously published about this research in a story titled “Researchers Discover a Method to Cross the Blood-Brain Barrier and Treat Lethal Tumors” which can be found here. The study was originally published in the scientific publication Journal of Controlled Release. You can read the abstract of the study here

What Happened?

Brain tumors such as glioblastoma are among the most lethal of cancers, and most patients don’t survive more than 15 months or so following their diagnosis. This is because many standard cancer treatments are not effective for these cancers. A primary reason for this is the blood-brain barrier, which protects the brain from toxic substances, like chemotherapy agents and most other cancer drugs. In this study, a team of scientists sought to find a way to bypass the blood-brain barrier in order to treat brain tumors like glioblastoma safely and effectively.

The focus of this research was on a specific peptide that is able to cross membranes and tissues like the blood-brain barrier, which is effectively a dense matrix of blood vessels and tissue. Peptides are a chain of linked amino acids. The scientists tinkered with the peptide by incorporating fluorine molecules and adding a staple between the amino acids. Previous research conducted by the team had found that this method could improve the ability of the peptide to bypass the blood-brain barrier.

Then the researchers were able to attach a cancer therapy to the modified peptide and set up a trial using a mouse model of brain cancer. They had a control group of mice treated with the drug and the regular, unmodified peptide and then a second group that received the drug attached to the enhanced peptide. The drug and enhanced peptide combination was dubbed M13.

Mice that received M13 saw cell death in the cells of their brain tumors while the normal brain cells were unaffected. This led to a 50 percent increase in survival rate among these mice. The team concluded that they had pioneered an effective method to deliver cancer drugs to the brain by bypassing the blood-brain barrier.

About Glioblastoma

Glioblastoma is a rare brain cancer. It is also the most aggressive cancer to originate in the brain. It is characterized by its rapid progression and poor response to most treatments. In most cases, the cause of glioblastoma is not known. A small number of cases evolve from another type of tumor called an astrocytoma. Risk factors for glioblastoma include genetic disorders such as Turcot syndrome and neurofibromatosis, exposure to pesticides, smoking, and a career in petroleum refining or rubber manufacture. Symptoms of glioblastoma include personality changes, headaches, memory loss, seizures, vomiting, and nausea; patients may lose consciousness in late stages. Treatment approaches include anticonvulsants, steroids, chemotherapy, radiation, and surgery. While a small number of patients can survive for several years, treatment is often ineffective, with the tumor relapsing quickly. Five year survival rate is only three percent. To learn more about glioblastoma, click here.

Why Does it Matter?

The deadly nature of brain tumors like glioblastoma means that there is a dire need for more effective strategies in terms of treatment and drug delivery. The authors of this study appear to have found a way to deliver cancer drugs to the brain safely and effectively, making tumors in the brain much more vulnerable:

“We have shown for the first time that the linking of an anti-cancer drug to a macrocyclic cell-penetrating peptide leads to effective dosing in mice at many times higher than the drug alone, which can significantly extend survival.” – Jorge L. Jimenez Marcias, Study Author, Postdoctoral Fellow

This breakthrough could potentially open up brain cancers to a wider variety of treatments that could start improving survival and outcomes for people diagnosed with these aggressive cancers.

“We were not only able to get a drug into the brain, but to deliver it at a concentration that should be able to kill tumor cells.” – Sean Lawler, Study Author, Associate Professor of Pathology and Laboratory Medicine, Brown University

These findings are a critical steppingstone to further refinement of this innovative method that could be a real game changer in glioblastoma and brain cancers in general. Continued research will entail continued tweaking and optimization of both the delivery method and the drugs being used. 

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