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Ruben Dagda, Pittsburgh Medical Technology Examiner
Making the blood brain barrier more permeable may be the answer
Although there is currently no cure for treating Parkinson's and Alzheimer's disease, a preclinical study published yesterday at the prestigious Journal of Neuroscience may revolutionize the way patients will be treated in the US. Currently, one of the major impediments for treating many neurodegenerative diseases is the fact that the blood brain barrier is highly impermeable to most FDA approved and experimental drugs. Therefore, only a small fraction of the drug reaches the brain and has a therapeutic effect.
However, scientists from Cornell University discovered a way to make the blood brain barrier more permeable so that the brain absorbs a higher amount of therapeutic drugs: by using adenosine agonists. In brief, scientists discovered that mice intravenously injected with drugs that stimulate adenosine receptors (NECA) were able to accumulate a higher amount of an experimental sugar molecule (dextran) in the brain upto three times more compared to untreated animals. The modified sugar stayed in the brain upto 24 hrs. following a single intravenous injection of the adenosine receptor agonist drug. The effect of the drugs on the blood brain barrier is specific for adenosine receptors since mice that lacked adenosine receptors did not accumulate the dextran in the brain.
What is the medical relevance of this study?
A pathological hallmark of Alzheimer's disease is that patients accumulate protein garbage in neurons called beta-amyloid and tau protein which is associated with the destruction of memory neurons. Using a mouse model of Alzheimer's disease, the scientists showed that mice co-injected with adenosine agonists and with beta amyloid busters (a monoclonal antibody called 6E10) were able to bind to beta amyloid deposits in mice. This experiment is a proof of principle for using drugs that can make the blood brain barrier and with FDA approved drugs for Alzheimer's disease such as acetycholinesterase inhibitors. This study is promising and can lead to the creation of new revolutionary therapies for treating Alzheimer's disease.
Approximately about 5.5 million people are afflicted with Alzheimer's and Parkinson's disease in the US. Many patients over 65 years of age are relegated to spending their final days of life in nursing homes or are cared by family members which can be a great economic and emotional burden.
There is a great need for finding safe and efficient techniques to administer drugs that can penetrate the blood brain barrier in high concentrations. Nowadays, some patients undergo highly invasive techniques such as direct injections of drugs into the ventricles of the brain, epidural injections or installing intracranial pumps to treat neurodegenerative diseases. Also, most drugs need to be chemically modified so that it can reach the blood brain barrier but renders the drug also capable to concentrate in unwanted tissues.
But what if we can avoid all this hassle and inconvenience of undergoing painful surgical procedures or spending a high amount of money on drugs that do not reach the brain? For instance about less than 10% of Parkinson's disease drugs such as Levodopa in combination with Carbidopa reach the brain while the rest is metabolized and wasted in Parkinson's disease patients. The solution proposed by the authors could bring down the costs of anti-neurodegenerative drugs and increase patient compliance.
The only downside is that patients will not be able to drink coffee or other caffeinated products if adenosine analogues or the FDA approved Lexiscan is used as treatment for Parkinson's and Alzheimer's.
Carman, A., Mills, J. Krenz, A., Kim, D. Bynoe, M. Adenosine receptor signaling modulates permeability of the blood-brain barrier, 2011, The Journal of Neuroscience 31(37): 13272-13280.
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