New technique bypasses the blood-brain barrier to deliver neuroprotection.


The blood-brain barrier represents a fundamental limitation in treating neurological disease because it prevents all neuropeptides from reaching the central nervous system (CNS). Currently, there is no efficient method to permanently bypass the blood-brain barrier.  Now, researchers at Harvard Medical School and Boston University have successfully shown neuroprotection in a Parkinson’s mouse model using a new technique, known as nasal mucosal grafting, to deliver drugs across the blood-brain barrier. The team state that their findings lend hope to patients around the world with neurological conditions that are difficult to treat due to a barrier mechanism that prevents approximately 98 percent of drugs from reaching the brain and central nervous system.  The study is published in the journal Neurosurgery.

Previous studies show that nasal mucosal grafting is a technique regularly used in the ENT field to reconstruct the barrier around the brain after surgery to the skull base. ENT surgeons commonly use endoscopic approaches to remove brain tumours through the nose by making a window through the blood-brain barrier to access the brain. Once they have finished the treatment, they use adjacent nasal lining to rebuild the hole in a permanent and safe way. The safety and efficacy of these methods have been well established through long-term clinical outcomes studies in the field, with the nasal lining protecting the brain from infection just as the blood brain barrier has done.  The lab chose to test their delivery method with GDNF because the therapy has been shown to delay and even reverse disease progression of Parkinson’s disease in pre-clinical models.

The current study used nasal mucosal grafting to deliver glial derived neurotrophic factor (GDNF) to the brains of a Parkinson’s mouse model. Data findings showed through behavioural and histological data capture that their delivery method was equivalent to the direct injection of GDNF, the current gold standard for delivering this drug in Parkinson’s disease, despite its traumatic nature and high complication rates.

The group explain that they saw an opportunity to apply these techniques to the widespread clinical dilemma of delivering drugs across the barrier to the brain and central nervous system. They go on to conclude that by functionally replacing a section of the blood-brain barrier with nasal mucosa, which is more than 1,000 times more permeable than the native barrier, surgeons may create a ‘screen door’ to allow for drug delivery to the brain and central nervous system.

The team surmise that their technique has the potential to benefit a large population of patients with neurodegenerative disorders, where there remains a specific unmet need for blood-brain penetrating therapeutic delivery strategies.  They go on to add that brain diseases are notoriously difficult to treat due to the natural protections the body builds against intrusion.  For the future, the researchers state that they see this expanding beyond Parkinson’s disease, as there are multiple diseases of the brain that do not have good therapeutic options.

Source: Massachusetts Eye and Ear

 

Illustrated concept of delivery method for drugs used to treat a variety of central nervous system diseases. The drugs may be administrated through the nose and diffused through an implanted mucosal graft (A, in red) to gain access to the brain. Under normal circumstances, there are multiple layers within the nose that block the access of pharmaceutical agents from getting into the brain, including bone and the arachnoid membrane, which represents part of the blood-brain barrier (B). After endoscopic skull base surgery, all of these layers are removed and replaced with a nasal mucosal graft (C ), which is 1,000 times more porous than the native blood-brain barrier. Consequently, the grafts may be used to deliver very large drugs, including proteins, which would otherwise be blocked by the blood-brain barrier. Design and illustration by Benjamin Bleier, M.D., and Garyfallia Pagonis.

Illustrated concept of delivery method for drugs used to treat a variety of central nervous system diseases. The drugs may be administrated through the nose and diffused through an implanted mucosal graft (A, in red) to gain access to the brain. Under normal circumstances, there are multiple layers within the nose that block the access of pharmaceutical agents from getting into the brain, including bone and the arachnoid membrane, which represents part of the blood-brain barrier (B). After endoscopic skull base surgery, all of these layers are removed and replaced with a nasal mucosal graft (C ), which is 1,000 times more porous than the native blood-brain barrier. Consequently, the grafts may be used to deliver very large drugs, including proteins, which would otherwise be blocked by the blood-brain barrier. Design and illustration by Benjamin Bleier, M.D., and Garyfallia Pagonis.

 

 

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