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Acoustic Therapy

June 1, 2015 | A version of this story appeared in Volume 93, Issue 22

The promising effects of ultrasonic waves—after harnessing the action of a fluorinated contrast agent—on amyloid plaque clearance are doubtless stimulating and of potential therapeutic value (C&EN, March 16, page 5). But the article and the original research ignore the physicochemical corner highlighted in other recent research, which unveils a complex issue.

Amyloid fibrils undergo breakage after long irradiation times, resulting in shorter chains of uniform size. However, fibril formation is also triggered at short irradiation times by a reagglomeration step similar to the one found in ultrasound-induced nucleation, and the process is pH-dependent (Nature 2005, DOI: 10.1038/nature03986; Proc. Natl. Acad. Sci. USA 2009, DOI: 10.1073/pnas.0901422106).

Molecular dynamics simulations also shed light on mechanistic details. Fibril disruption occurs at negative pressures as bubbles are created and then undergo collapse, mainly near the hydrophobic residues of the transmembrane region. Fragmentation of shorter amyloids will require longer irradiation times because the number of peptide residues is insufficient to serve as bubble nuclei (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja502749f).

It is true, as noted, that focused ultrasound may disrupt the blood-brain barrier, but minor damage has been observed at the kilohertz range in monkey models (Cancer Res. 2012, DOI: 10.1158/0008-5472.can-12-0128). Certainly, extra studies will be needed, but chemistry with sound waves should be more than a passive spectator. I like the anonymous aphorism that most key discoveries invariably emerge as something new from the past.

Pedro Cintas
Badajoz, Spain



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