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A fishy approach to treating brain tumors
Researchers say lampreys might hold the key to getting mammalian brain tissue to accept chemotherapy drugs.
It's a rare veterinarian who would see a lamprey in practice, but researchers at the University of Wisconsin-Madison and University of Texas at Austin are digging into some of the animal's antigen receptors to explore a new path to treating cancer in the brain.
What's a lamprey again?
Lampreys, according to our mutual friend Wikipedia, are sometimes inaccurately called “lamprey eels” but are actually a jawless fish. The adult lamprey may be characterized by a toothed, funnel-like sucking mouth.
It all starts with the pesky blood-brain barrier (BBB), which, in an undisrupted state, makes it hard to get and keep therapeutic drugs near a brain tumor. Researchers noted in a May 15 article in Science Advances, however, that certain events and pathologies-like trauma, stroke, tumors, multiple sclerosis, high-frequency focused ultrasound and osmotic agents-can disrupt the BBB. These moments expose the normally inaccessible brain extracellular matrix (ECM) to circulating blood components (like, you guessed it, cancer drugs).
So, what if a drug vector could show similar results working within normal ECM?
“This strategy is potentially superior to therapies directed against cell-intrinsic targets because normal brain ECM serves as the targeting ligand rather than cell-associated disease variants or markers that are often altered or lost after treatments, resulting in therapeutic resistance,” researchers write.
This is where lampreys come in. Researchers note that lamprey antigen receptors known as variable lymphocyte receptors (VLRs) could have advantages over standard peptides and antibodies as ECM-targeting reagents in drugs. Their biggest selling point? These VLRs are separated by roughly 500 million years of evolutionary distance, so they can slip in where mammalian antibodies can't and keep the drugs in and around cancer tissue longer.
Researchers tested the VLRs with the chemotherapy drug doxorubicin on mice with glioblastomas (GBMs).
“The VLRs identified in our work bind normal brain ECM and strategically use the pathological exposure of normal ECM for targeting specificity,” the researchers write. “This approach could therefore obviate the need to identify a disease-specific target, and the ECM-targeting VLRs could be customized for any neurological disease that exhibits BBB disruption (or via artificial BBB disruption) by simply altering the therapeutic payload.”
Without making specific claims about particular use in human or veterinary medicine, the researchers' hope is that further study into these unique drug-carrying VLRs could “provide a new approach for treating many debilitating neurological diseases that currently lack effective treatments, including incurable GBM.”