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Delivering cancer treatment via the cerebrospinal fluid

by Ioannis Mountziaris

This summerizes a talk by Dr. James Rubenstein, MD, PhD

Brain cancer serves up a challenge for treatment: radiation therapy is extremely damaging to the brain, and chemotherapeutics have difficulty crossing the blood-brain barrier. While modern drugs can specifically target of cancer cells, their delivery to the immune privileged compartment of the central nervous system has been a challenge. Dr. James Rubenstein of UCSF is interested in an alternative approach: utilizing the brain’s unique vasculature to directly deliver drugs to target central nervous system lymphomas. Dr. Rubenstein’s research focuses on drug delivery via the cerebrospinal fluid (CSF), the liquid that bathes the brain, protects it from mechanical shock, and ensures chemical stability.

Using a catheter connected to a lateral ventricle of the brain, Dr. Rubenstein is able to deliver Rituximab, a clinically approved anti-CD20 monoclonal antibody used to treat lymphomas, directly into the CSF. Through this procedure, Dr. Rubenstein is able to circumvent the blood-
brain barrier, and deliver a relatively large drug (>140 kDa) to the brain, something not easily possible from the blood.

While Dr. Rubenstein presented a powerful case for Rituximab delivery via the CSF, he also mentioned the limits of this treatment. While delivering Rituximab is possible, the drug is cleared from the brain within hours of treatment, requiring repeated administration. In addition, this treatment is limited; patients were found to build resistance to Rituximab over time. It is clear that there is still work to be done to optimize CSF drug delivery, as well as optimize drugs for function in the immunologically privileged brain.

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