One of the medical challenges with diseases of the brain is getting any treatment to cross the blood-brain barrier, however tests on the brains of mice with Alzheimer’s traits, has shown it is possible to use the body’s own natural delivery system to get manufactured treatments absorbed by the brain.
Dr. Matthew Wood stated in the research:
“These are dramatic and exciting results. This is the first time this natural system has been exploited for drug delivery. We are working on sending exosomes to muscle, but you can envisage targeting any tissue. It can also be made specific by changing the drug used.”
Currently, less than 5% of drugs (made up of very small molecules) are able to cross the barrier; one example is temozolomide, which is the only chemotherapy available for treating brain tumours such as glioblastoma multiforme and progressive anaplastic astrocytoma. These tumours have a poor prognosis and continue to grow, even after treatment with temozolomide. Therefore, new therapies for these hard-to-treat brain tumours are needed urgently alongside brain malfunctions such as Alzheimer’s, Parkinson’s and more.
This natural barrier exists to protect the brain, preventing bacteria from crossing over from the blood, while letting oxygen through. However, this has also produced problems for medicine, as drugs can also be blocked. Researchers used the body’s own transporters, exosomes, to deliver drugs and proved to be quite successful.
The team at Oxford harvested exosomes from mouse dentritic cells, part of the immune system, which naturally produce large numbers of exosomes. They then fused the exosomes with targeting proteins from the rabies virus, which binds to acetylcholine receptors in brain cells, so the exosome would target the brain.
They filled the exosomes with a piece of genetic code, siRNA, and injected them back into the mice. The siRNA was delivered to the brain cells and turned off a gene, BACE1, which is involved in Alzheimer’s disease.
The authors reported a 60% reduction in the gene’s activity.
This could be a groundbreaking advancement in the treatment of debilitating Alzheimer’s disease and thought leaders on the subject are excited by these new studies. Dr. Susanne Sorensen, head of research at the Alzheimer’s Society, said:
“In this exciting study, researchers may have overcome a major barrier to the delivery of potential new drugs for many neurological diseases including Alzheimer’s. The blood-brain barrier had been an enormous issue as many potential drugs have not been properly tested because you couldn’t get enough of them into the brain. If this delivery method proves safe in humans, then we may see more effective drugs being made available for people with Alzheimer’s in the future.”
Dr Simon Ridley, head of research at Alzheimer’s Research UK, adds: “This is innovative research, but at such an early stage it’s still a long way from becoming a treatment for patients. Designing drugs that cross the blood brain barrier is a key goal of research that holds the promise of improving the effectiveness of Alzheimer’s treatments in the future.”
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Written by Sy Kraft, B.A.