MUSC’s first preclinical use of BrainPath technology drives major PDX brain tumor model development

In a field with notoriously poor outcomes, MUSC neurologists have developed a new brain cancer model to help to address challenging clinical problems. Neuroscientist Arabinda Das, Ph.D., and neurosurgeon Bruce Frankel, M.D., have developed the first clinically relevant patient-derived xenograft (PDX) brain tumor model using NICO Corp.’s BrainPath Automated Preservation System.

BrainPath is a critical technology in minimally invasive parafascicular surgery, or MIPS, which allows neurosurgeons to reach deeper brain lesions safely with minimal disruption to the surrounding healthy brain tissue. Cleared by the FDA in 2012, the instrument was first used at MUSC in 2015. While BrainPath is now used in many of the top operating rooms across the country, MUSC is the first to employ this cutting-edge technology in an animal model.

Das, assistant professor in the Neurosurgery Department, researches adult and pediatric primary malignant brain tumors and brain metastasis originating from other primary tumors. He is collaborating with Frankel to perform parallel preclinical studies using similar methods to what neurosurgeons use in the operating room.

How BrainPath improves brain surgery

 

Aggressive brain cancers such as glioblastoma continue to have a particularly grim prognosis, with a five-year survival rate of less than 10%. Surgery is the standard of care for most brain tumors. Previously, the balance between preserving the healthy brain tissue and removing all of the tumor was more challenging.

BrainPath combines imaging and computerized brain navigation systems to move along the brain’s natural folds and fibers, which allows surgeons to find and reach deeper tumors safely. This reduces patient recovery time, which translates to lower patient costs and improved quality of life.

Even though surgical resection is the standard of care for patients with glioblastoma today, most preclinical models only focus on the pharmaceutical treatment of solid intracranial tumors, said Das. “The lack of resection and recurrence models has undermined the efforts in improving treatment for this brain disease. That’s why this surgical resection model is important since it recreates the postsurgical tumor microenvironment.”

For the purpose of obtaining brain tissue samples, BrainPath has three main benefits compared with other instruments used in the operating room. It is fully automated, which standardizes intraoperative tissue collection. There is also increased brain tissue yield compared with conventional methods and improved biological preservation of the collected tissue due to precise regulation of the temperature and preservation solution, said Frankel.

Preclinical use accelerates patient improvements

With help from BrainPath’s inventors at NICO Corp., the neuroscientists now have a modified device for use on preclinical mouse models. Das and Frankel plan to run parallel clinical and preclinical studies using this device, which have the potential to lead to pivotal changes.

“Our surgical resection model recreates the postsurgical tumor microenvironment and is a reliable model for adjuvant therapy evaluation. Generating data in animal models can provide rapid and valuable solutions, which can then be translated into the clinic to help patients,” said Frankel.

Frankel uses BrainPath to get the brain tumor tissue from his patient, and it is then put directly into a humanized mouse, with minimal manipulation. This generates the PDX model. Once the tumor is established in the mouse, multiple clinically relevant questions can be addressed.

“Importantly, BrainPath allows us to perform serial biopsies of brain tumors in the animal models. This has never been attempted and will provide valuable information.”
— Dr. Arabinda Das

“Importantly, BrainPath allows us to perform serial biopsies of brain tumors in the animal models,” said Das. “This has never been attempted and will provide valuable information.”

This improved and more reliable PDX model allows the scientists to evaluate how treatment alters the complex brain microenvironment, including tissue mutations within the tumor during treatment or brain tumor development. It also helps the clinicians to examine the best timing for surgery and treatment. This timing is critically related to efficacy and patient outcomes.

“BrainPath allows us to get human brain tumor tissue that is histologically intact with the same genetic signature as what was in the patient. This is important because the samples will then grow in a physiologically relevant tumor microenvironment,” said Das.

MUSC has a three-year sole-use agreement with NICO for the preclinical use of the device. During that timeframe, Das and colleagues plan to expand this technique to study other primary and metastatic adult and pediatric brain tumors. Also, an innovative approach such as this will help the team to secure the necessary funding to continue to improve patient outcomes, he said.

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