One of the most difficult problems in treating neurological or psychiatric disorders is the inability to get drugs into the brain to reach their target area due to the blood-brain barrier. The blood-brain barrier, as the name suggests, is the highly selective barrier that separates the brain from circulating blood. The BBB prevents close to 98 percent of drugs from crossing over and entering the brain, which can be extremely problematic in treating diseases such as Parkinson's, which are neurological in nature. However, a group of researchers at Harvard Medical School and Boston University may have figured out a technique to solve this conundrum.
One previous way of treating diseases such as Parkinson's to bypass the BBB is a direct injection of whatever drug into the brain, which can be very traumatic and complicated. In the new way, by experimenting on rats, they used a procedure known as nasal mucosal grafting that is regularly used by ENTs. In this technique, they cut a small window into the BBB to gain access to the brain, and then use lining from the adjacent nasal cavity to seal the hole back up. The nasal lining is 1000 times more permeable than the BBB, so drugs are much more able to freely pass through. They also mentioned that despite the increased permeability, it has been shown in long-term clinical studies that the nasal mucosa still protects the brain from infections.
This technique could have huge implications in treatment of many of the nasty neurodegenerative diseases we hear about, including Parkinson's, Alzheimer's, Huntington's, and ALS, without the trauma and complications associated with previous methods.
Link to article: https://hms.harvard.edu/news/bypassing-blood-brain-barrier?utm_source=twitter&utm_medium=social&utm_campaign=hms-twitter-general
What a creative way to utilize the patient's own tissues! I had a previous post about Ommayas (which are plastic catheter devices inserted through the dura into the ventricles for chemotherapy administration). I wonder if the nasal mucosal grafting can also be used for chemotherapy administration, as in the Ommaya.
ReplyDeleteAlso, what happens to the nasal mucosa over a long period of time? You mentioned that the mucosal lining still protects the brain from infections, but does this mucosal tissue get "replaced" by the meningeal type of tissues over time? How does the mucosal lining stay in tact?
Those are all really good questions. Those would all be aspects that should be tested before this technique is being used frequently, but many of those questions would require long trials in order to discern any results. Probably the most important would be what happens to the nasal lining over time. If it is shown to wear down over time and the patient would need another procedure depending on age, would it be worth doing the first time? As far as how the graft remains in place, it looks like they just peel back the arachnoid and dura maters, and then inset the graft against the pia mater. When they put the arachnoid and dura back down, they set over the graft and hold it in place. As far as the mucosal graft being replaced with meningeal tissue over time, I don't think it would. This would need to be tested, but the purpose of this initial experiment was just to see if the graft could allow better permeability for drugs to cross the BBB. However, I don't think meningeal tissue would spontaneously grow over and around the graft and occlude it. After a little digging, I was able to find the full-text article if you'd like to read a little more.
ReplyDeleteLink to full-text article: http://ovidsp.tx.ovid.com/sp-3.17.0a/ovidweb.cgi?WebLinkFrameset=1&S=CAPKFPCJFPDDALBNNCJKIGMCPBAEAA00&returnUrl=ovidweb.cgi%3f%26TOC%3djb.search.31%257c1%257c50%26FORMAT%3dtoc%26FIELDS%3dTOC%26S%3dCAPKFPCJFPDDALBNNCJKIGMCPBAEAA00&directlink=http%3a%2f%2fgraphics.tx.ovid.com%2fovftpdfs%2fFPDDNCMCIGBNFP00%2ffs046%2fovft%2flive%2fgv023%2f00006123%2f00006123-900000000-97547.pdf&filename=Heterotopic+Mucosal+Grafting+Enables+the+Delivery+of+Therapeutic+Neuropeptides+Across+the+Blood+Brain+Barrier.&PDFIdLinkField=%2ffs046%2fovft%2flive%2fgv023%2f00006123%2f00006123-900000000-97547&link_from=jb.search.31%7c1&pdf_key=B&pdf_index=jb.search.31&D=ovft
An article I read on this same topic talks about a similar procedure where they inserted nano-particles through "temporary portals" in the BBB and were able to use ultrasound to localize the nano-particles to the specific location where the tumor was. This is very interesting to me, and a great advance in the science and medical world. While I am glad the BBB has been broken and thankful for all the advances it will give, it worries me a little to see the extent to which we can manipulate such a carefully laid out defense. Are we too excited in this discovery that we are not concerned with the repercussions? For, if we are making the BBB more permeable to drugs, we are certainly making it more permeable to other toxins and molecules which have been prevented from entering the nervous tissue due to the specificity of the BBB. The article I linked below says the following, "Essentially, we are turning the BBB into our friend as opposed to our enemy." Now, I am all for the use of this discovery to treat things otherwise untreatable (brain tumors etc) but perhaps a better approach to this would not to view the BBB as a friend. The goal of the BBB is to protect the brain and to provide a solid defense against unwanted invaders. Our goal is to manipulate it into letting in choice molecules that we believe would better the race. As the goals are quite different, perhaps it is best to approach the BBB not with "friendship" but with respect, understanding, and research into the so called butterfly effect of our actions.
ReplyDeleteThis is a cool breakthrough. It reminds me of an article I was reading a couple of months ago where BBB was discussed in terms of even our own neurotransmitters, such as dopamine. Dopamine cannot pass through the BBB. However, endocannabinoids, also produced by the body, can pass through the BBB. I like this idea of physically avoiding the BBB for treatments, but as commented by some others, physically removing the BBB seems to have some implications that could lead to undesirable results or repeat procedures. I'm curious how far away we are from understanding a better way of avoiding the BBB chemically, versus having to physically avoid it, but again this looks like it's at least on the right track. Source: https://www.washingtonpost.com/news/to-your-health/wp/2015/10/08/scientists-runners-high-like-marijuana-high/
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