I wrote a couple of years ago here about the idea of making the blood-brain barrier more permeable by the use of focused ultrasound, in the presence of injected microbubbles. This would be a very useful thing if it works – as anyone who’s been concerned with central nervous system drugs (or drug delivery in general) well appreciates, the lining of the cerebral blood vessels is tight enough to send a lot of potentially useful therapies bouncing off it. The brain is a well-protected organ, and all sorts of schemes have been hatched over the years to get compounds past that last line of defense.
Since writing that post, I’d been wondering how the ultrasound idea had been working out, so I was particularly interested to see a recent exchange in the pages of PNAS. This paper (from a team of NIH researchers) is a detailed study of rat brain tissue after exposure to the technique, and they find a variety of markers of injury and inflammation at the site of ultrasound exposure. In fact, they go as far as to say that the entire process is hard to distinguish from ischemia or head trauma, and advocate caution before any further use of it in human clinical trials.
That’s a bucket of cold water, for sure, and the paper drew a published response from a team of researchers in Toronto who have been working in this area for years now. They suggest that the NIH paper is wrongly interpreting their results – that there are several markers of ischemic damage, etc., that are not induced by the ultrasound treatment, that no cell death is noted (and no scar tissue, etc.), and that the inflammatory markers resolve within hours to days. Buried inside their response is a note that the NIH group, they say, used five to ten times the recommended concentration of microbubbles.
That one drew a further response from the NIH team. The entire exchange, I should note, is conducted in flawless high academic style – the Toronto group thanks the NIH people for publishing their results, which they say confirm their own work (before then getting down to the disagreements, in the unsaid “If you’d only done this properly” style). The NIH group in turn thanks the Toronto one for their response, which they say now gives them a chance to expand on the implications of their own work (in the unsaid “If you’d only understood what we wrote” style). They say that the Toronto reply misses out on a number of details of the microbubble preparation and the ultrasound technique used, and that they did not, in fact, use any sort of large excess of microbubbles, and made sure that they were well below the ultrasound levels that are known to cause tissue damage on their own, etc. They also point out that if this technique is actually going to be used in human trials for neurodegenerative diseases, that the patients involved will have to have much larger areas of their vasculature sonicated (just to get enough drug through).
So there the matter stands. At the very least, everyone can agree that (as the phrase goes) “more study is needed”. Who will be vindicated at the end of that study is too early to say, but given the (appropriate) caution needed when messing with the blood vessels around someone’s brain, I’d say that it might be a while before we see this technique applied. . .