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Delivery Technique Devised to Cross Blood-Brain Barrier

Brain synapses illustration

(Allan Ajifo, Wikimedia Commons)

21 October 2015. Medical researchers developed a technique that allows drugs for treating neurological disorders to penetrate the blood-brain barrier, a difficult obstacle up to now. The team led by ear, nose, and throat, or ENT, specialist Benjamin Bleier at Massachusetts Eye and Ear Hospital and Harvard Medical School described its methods with lab mice in a recent issue of the journal Neurosurgery (paid subscription required).

Blood vessels in the brain form a support network for brain functions, with tightly-packed cells lining blood vessels that allow nutrients to pass through, but keeping out foreign substances. This barrier also keeps out drugs to treat neurological conditions, such as Parkinson’s or Alzheimer’s disease. So far, no efficient method is available to penetrate this barrier that prevents some 98 percent of current drugs from reaching the brain or central nervous system.

Bleier and colleagues from Mass. Eye and Ear, Harvard Medical School, and Boston University sought to adapt a technique from ENT surgery to help drugs overcome this obstacle. The technique, known as nasal mucosal grafting, is used to rebuild a hole in the base of the skull through the nose, after removing a brain tumor with endoscopes that operate safely inside the brain. Nasal mucosal grafting takes tissue from nearby nasal passages to rebuild the hole, preventing infections to occur, one of the protections provided by the blood-brain barrier.

The researchers tested the hypothesis that a nasal mucosal graft could also allow drugs to cross the blood-brain barrier, while still protecting the brain from harmful substances. They tested the technique in lab mice, with a therapeutic protein called glial-derived neurotrophic factor or GDNF, considered a promising treatment for preventing or reversing the advance of Parkinson’s disease. The Michael J. Fox Foundation for Parkinson’s Research funded the project.

In their study, the team performed nasal mucosal grafts on lab mice induced with Parkinson’s disease, and delivered doses of GDNF through the grafts. The researchers then compared the therapeutic effects of those GDNF doses to GDNF injected directly into the brains of similar mice, as well as other mice receiving a saline-solution placebo. The authors say direct injections into the brain, while possible today, face a risk of complications.

Bleier’s group measured the amount of cells in the substantia nigra, a part of the brain sends that sends nerve fibers deep into both sides of the brain, and where neurotransmitters controlling movement and coordination are located. People with Parkinson’s disease often have diminished substantia nigra cells. The findings show mice receiving GDNF through nasal mucosal grafts had about the same amount of substantia nigra cells as mice receiving GDNF injections, but more than mice receiving a placebo. In addition, after seven weeks, mice with nasal mucosal grafts had motor skills equivalent to mice receiving injections.

While the study focused on a treatment for Parkinson’s disease, Bleier believes nasal mucosal grafts can be applied to a wide range of disorders. “We are developing a platform that may eventually be used to deliver a variety of drugs to the brain,” says Bleier in a Mass. Eye and Ear statement. “Although we are currently looking at neurodegenerative disease, there is potential for the technology to be expanded to psychiatric diseases, chronic pain, seizure disorders and many other conditions affecting the brain and nervous system down the road.”

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