Research interest is building over the possibility of using viruses to transport drugs and genes across the “blood-brain barrier” to non-invasively treat brain cancer and other neurological disorders such as Alzheimer’s and Huntington’s diseases, and a Mayo Clinic research team is staking out an intellectual property position in the field.
 
The blood-brain barrier (BBB) is a semipermeable blockade of tightly packed cells that is crucial to keep pathogens and potentially harmful chemicals circulating in the blood from entering the brain and spinal cord. Its existence assures that the central nervous system functions property.
 
But the BBB also blocks out about 95 percent of medicine delivered orally or intravenously: Potentially therapeutic genetic and drug therapies for brain cancer and degenerative neurological diseases are too large pass through. As a result, doctors often must resort to injecting drugs directly into the brain after drilling into the skull. In addition to being costly and extremely invasive, this method limits a drug’s effectiveness and can cause irreversible damage to an already-damaged brain.
 
While huge investments are being poured into developing drug candidates and genetic therapies to treat aggressive brain cancers, Alzheimer’s and Huntington’s, pharmaceutical companies and other funders have not shown nearly as much interest overcoming this “bottleneck” in their delivery methods. That, however, could be changing as animal testing by researchers at Mayo, the California Institute of Technology, Johns Hopkins and elsewhere is demonstrating it can be done effectively by piggybacking drugs onto harmless viruses.
 
For instance, a Mayo team led by Dr. Robert B. Jenkins, a professor of laboratory medicine and pathology specializing in brain cancer genetics, has been reporting success at penetrating the BBB in mouse models using a proprietary synthetic peptide carrier as a delivery vehicle for chemotherapy drugs and other neurological medications.
 
In 2014, they announced they were able to transport the drugs without modifying any of the molecules involved using a viral vector and a synthetic peptide called K16ApoE, which binds to proteins in the blood to create entities that can pass through the blood-brain barrier by creating temporary pores through which various molecules can be transported to the brain.
 
They called their system “the least complicated, least expensive and most versatile method for delivering therapeutics to the brain.” It builds on previous successes of delivering antibodies targeted against amyloid plaques into the brains of mouse models of Alzheimer’s disease using the same method.
 
The next year, the Jenkins lab published further evidence of the efficacy of using the K16ApoE peptide in the Journal of Neuro-Oncology, in which they reported that the brain uptake of substances delivered into mice was more than 40 times greater with the peptide than without. That led the Mayo researchers to conclude the results “suggest K16ApoE renders the BBB transiently permeable, which may be utilized for brain targeting of chemotherapy drugs.
 
“Thus, the method may offer a simple avenue for pre-clinical evaluation of drugs against brain cancer and potentially other neurological disorders.”
 
The Rochester clinic applied for patent protection for the K16ApoE method in July, and on Jan. 12, the U.S. Patent and Trademark Office officially published the application, naming as inventors Jenkins, researchers Gobinda Sarkar and Geoffrey Curran, Mayo associate neurology professor Charles L. Howe and research technologist Reghann LaFrance-Corey.
 
Their efforts at overcoming the blood-brain barrier for drug delivery are adding to a small-scale but growing momentum in the field, which seems likely to appeal to small companies rather than big pharma at this experimental point. For example, a method developed by Johns Hopkins researchers to produce a form of the anti-cancer drug that can pass through the BBB has been licensed to Dracen Pharmaceuticals Inc., a startup founded by the researchers themselves.
 
The Mayo BBB technology itself remained unlicensed as of last month, according to an update of the clinic’s biopharmaceutical portfolio. The research effort was supported by the clinic itself, Bernie and Edith Waterman and the Ting Tsung and Wei Fong Chao Family Foundation.