In a new study on mice, researchers show it is possible to deliver drugs to fight cancer and other diseases into the brain via the bloodstream using a small molecule to carry them. Reporting in the journal PLOS ONE, the team, from the Mayo Clinic in Rochester, MN, says the synthetic peptide carrier can ferry the drugs across the blood-brain barrier without them having to be modified.
First author Dr. Gobinda Sarkar, a neuroscientist at the Mayo Clinic, says: "Not only have we shown that we can transport eight different molecules, we think this method will be less disruptive or invasive because it mimics a normal physiological process."
The team believes its work will be of great interest to drug developers making and testing new drugs to fight brain cancer and other neurological diseases.
The blood-brain barrier prevents unwanted agents and pathogens from crossing over into the brain from the bloodstream. In that respect, it does a good job to preserve health. But when the brain is sick or develops a tumor, then this advantage becomes a disadvantage, in that it impedes access to treatment.
Without access via the blood-brain barrier, doctors treating brain diseases have to resort to invasive methods. These not only carry the risk of causing further brain damage, but they can also render drugs less effective.
Peptide binds to proteins and 'fools' blood-brain barrier receptors
Researchers say it may be possible to deliver drugs to fight cancer and other diseases into the brain via the bloodstream using a small molecule to carry them.
In earlier experiments with mouse models of Alzheimer's disease, the researchers had already successfully delivered antibodies across the blood-brain barrier to tackle amyloid plaques in the brain.
In this study, they investigated the synthetic peptide K16ApoE. Once injected into a vein, the peptide binds to proteins in the blood to make "pseudo-ligands" that "fool" the blood-brain barrier receptors into interacting with them.
The researchers believe the interaction between the receptors and the "pseudo-ligands" opens temporary pores in the blood-brain barrier that allow various molecules to pass through to the brain.
Using this method, the researchers transported a number of molecules across the mouse blood-brain barrier, including: cetuximab, cisplatin, methotrexate, three different dyes, and synthetic peptides Y8 and I-125.
Method meets three of the five requirements for a usable therapy
They believe their approach offers a versatile, simple, affordable way of delivering drugs to the brain, and note that it meets three of the five criteria for a usable therapy: "feasibility of repeated or continuous administration, easy introduction into clinical practice and usefulness irrespective of size and location of a tumor in the brain."
However, more work is needed to fulfill the other two requirements: how effective the method is and whether it has a favorable adverse effects profile.
They conclude that any future investigation will need to evaluate how well the K16ApoE method allows drugs to pass through the brain barrier to effectively treat patients with brain cancer and other brain-associated disorders.
Meanwhile, Medical News Today recently learned of a study from Harvard Medical School published in Nature that revealed insights into a little-known mechanism for opening and closing the blood-brain barrier. The team identified a gene in mice that may be responsible for limiting the barrier's permeability.