This month Jon Weingart discusses a novel way to get past the blood-brain barrier. Program notes: 0:20 Blood brain barrier keeps toxic substances out 1:20 Deliver ultrasound without opening the skin 2:21 Perhaps a skull implant 3:21 How long can it stay in place? 4:21 So many things implanted these days 5:16 No curative therapies […]
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00:00:00Welcome to this month's brain matters of elizabeth tracy and i'm john weingart professor of neurosurgery at johns hopkins hospital John we've got a really interesting and kind of a basic science thing we're going to talk about this month help me out we're talking about an article that deals
00:00:14with the blood brain barrier a layer between the blood stream on the brain it protects the brain from toxic substances Getting through the problem for disease problems is that it also keeps medicines from getting into the brain and over time there have been a number of efforts to
00:00:32disrupt that layer to try to get substances in The approach we're talking about today is disrupting the blood brain barrier The ultrasound technology which we're talking about today uses sound waves to disrupt that barrier and that technology has been investigated for ten or fifteen years in this particular
00:00:51study In addition to the focused low intensity ultrasound waves they use micro bubbles in the circulation those micro bubbles when the sound waves hit them start to vibrate which then adds to the disruption of the blood brain barrier And so this particular study looked at a approach in
00:01:10people where they placed the little ultrasound transducer into the skull and then they were able to deliver the ultrasound waves without opening the skin the skull and a human is too thick to deliver the ultrasound just through the skin so you do have to implant transducer into the
00:01:29skull in some way to deliver the ultrasound waves The trial measured disruption of the blood brain barrier with m r i scan and with the contrast agent that they give with mri's scans to see how muchmore of that contrast agent leaked into the area They did follow that
00:01:46up with delivering ah chemotherapeutic drug But there was no measurement of that drug in the brain It appears that they were able to demonstrate that with this implantable device they could safely deliver the ultrasound waves and disrupt the blood brain barrier over a small area for the kinds
00:02:03of tumors that the approach is targeted at Their volume is much larger So in terms of it really being beneficial one would have to expand out the size of the transducer Maybe multiple transducers replaced One could even hypothesize that one could put a skull implant in that had
00:02:22the different transducers built into the implant One interesting thing was that they were able to access the device with just a needle So from a technological point of view very clever that they could implant this ultrasound transducer and sort of turn it on with just a needle through
00:02:38the skin And are you persuaded by first of all the practical aspects of disrupting the blood brain barrier In your mind would that be advantageous Absolutely Because it would open up a much larger number of drugs that could be delivered to the brain It's really a drug delivery
00:02:56issue You have that silver bullet and you need a way to get it there Then maybe this is the best way to deliver it Because of that blood brain barrier drug delivery approaches One needs to spend as much attention on the drug delivery approaches as you do on
00:03:11selecting the appropriate drug for the treatment with regard to this one Then i hear you saying that you really think it was clever to develop a transducer that was needle accessible after it was implanted How long did those things stay in place And how troubling is it to
00:03:28actually implant them Looking at the report the implantation is a simple thing in terms of longevity of them they used them repeatedly I believe for three to four months sounds like it used to be used in conjunction than with other image ng so that the exact placement of
00:03:44the transducer would be possible exactly that the end of the day having some way to access how much drug is being delivered is critical once you have proof of principle that yes you can open the blood brain barrier The next step is to prove that yes your drug
00:03:59is getting in there two final questions one is these things they're implanted in the skull so they're actually housed within the bony area and that's where they stay for the whole time is that correct Yes that is correct And i just wonder about infection risk Well there's always
00:04:15going to be an infection risk with any time you put something foreign into the body but so many things aaron planted these days defibrillators for the heart stimulators for pain in the spinal cord infusion pumps for pain medicine and different things implants for defects prostheses for joints So
00:04:35there is a rift to putting those things in but it's a low risk it's really not a barrier to doing this type of work Previous research even that done right here in this department with biodegradable wafers implanted in the area of a tumor We know something about the
00:04:52efficacy of getting things beyond the blood brain barrier So if you were going to be a betting guy what would you say about the likelihood that this kind of technology or something similar would turn out to be practical with regard to that and even have the impact that
00:05:07we would like it to The high grade glioma which is what this treatment is targeted at is very resistant to a lot of different types of therapies in terms of curative therapy there are no cured of therapies for this problem however as a complement to other types of
00:05:23therapies other delivery strategies it could be very effective even for focused delivery of things and it could even be expanded to other neurodegenerative problems and with regard to those specific tumors though how efficacious have therapies that have been delivered beyond the blood brain barrier bin wafers or biodegradable
00:05:46polymers that deliver be seeinyou chemotherapy are approved worldwide they are effective at extending survival and increasing tumor control Over the years there have been a number of trials looking at conviction enhanced delivery to deliver larger molecules across the blood brain barrier in some patients there were remarkable responses
00:06:08responses that could never have been achieved by giving these compounds systemically namely because not only do they not get across the blood brain barrier but their toxic to other organs in the body so one advantage of putting things beyond the blood brain barrier even something that you could
00:06:24tragically open the blood brain barrier and get it quickly into the brain without giving a high dose of the drug may allow you to give compounds which are toxic to the rest of the body but now you could give them in a safe level still get a therapeutic
00:06:38level on the brain and not have added systemic toxicity excellent anything else you'd like to add about this one not at all that will do it all right that's this month's brain matter's i'm elizabeth tracy and i'm just wondering

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