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Transient Disruption of the Blood-Brain Barrier (BBB) by Modified Serum Albumin

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Principal Investigator



Organic Chemistry

Treating brain pathologies, including cancer, is particularly difficult due to the isolation of the brain by the blood-brain barrier (BBB). The BBB restricts or blocks the penetration of therapeutic agents (depending on type) to the brain, making it difficult to treat varying conditions (e.g. brain tumor). This limits options for treatment and necessitates the use of high or even extreme doses of drugs in the treatment of patients. Consequently, agents that transiently disrupt the BBB and allow safe passage of drugs to the brain would be useful for a variety of neuropathologies.

The present invention uses modified human serum albumin (HSA) in order to induce transient breakage of the BBB. Modified HSA can be used in combination with other agents, such as chemotherapeutic drugs, in order to increase their entrance to the brain. Thus, lower concentration of drugs can be used, while increasing treatment efficacy.


·         Transient BBB breakage – in vivo studies in rat models show no brain damage and complete BBB recovery after 1 week.

·         Minimally-invasive, local, non-toxic – high efficacy of action when using convection-enhanced delivery with no post-treatment toxicity.

·         Approved treatment – HSA is already an approved drug for various medical conditions.

·         Can be combined with other drugs, such as chemotherapeutic agents.

Technology's Essence

A collaboration between the Sheba Medical Center and Weizmann Institute of Science, Israel, found that modified human serum albumin can induce BBB breakage in a transient manner and with low toxicity to the brain. The research groups screened multiple modified HSAs in vitro and selected the most efficient one. In vivo experiments in rats bearing glioma brain tumors showed that administration of this modified HSA along with chemotherapy reduced tumor size. No hemorrhages or toxicity post-treatment were detected, and the BBB was completely recovered after 7 days.   

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