Variable lymphocyte receptors (VLRs) in the parasitic fish are being used for targeted delivery drug substances across the blood-brain barrier.
The sea lamprey is a parasitic fish that hold the key to the development of new drug delivery technology that can be used to treat brain disorders. The fish’s immune system is similar to that of humans, except rather than make antibodies, it produces variable lymphocyte receptors (VLRs) as part of its defense mechanism.
Researchers at the University of Wisconsin-Madison and the University of Texas at Austin have discovered that VLRs can cross the blood-brain barrier where blood-brain barrier disruptions occur – which happens when a disease is present – and deliver active drug substances to the site of the pathology.
The researchers vaccinated lampreys and identified VLRs that bind tightly to the brain’s extracellular matrix. The VLRs were conjugated to Doxil (doxorubicin, Johnson & Johnson) and administered to mice with glioblastomas; the survival time for the treated animals was significantly extended.
By targeting the extracellular matrix rather than the brain cells, the scientists believe this approach has the potential to allow the delivery of higher doses of drugs. The VLRs also only target damaged tissue and do not interact with healthy cells, reducing off-target and adverse reactions.
While the initial investigation focused on a lethal cancer, the researchers also hope the VLPs will be effective for delivery active payloads that can treat other neurological diseases and brain conditions, such as Alzheimer’s, multiple sclerosis, stroke and traumatic injuries.