Anavex Life Sciences Corp (AVXL)

[apostrophe]

re: "I found the ultrasound article interesting too, also AU research. Seems a shame they can't take a non-invasive therapy like that straight to human trials. "

No way I would volunteer for that. For one thing, I personally find the nerve jangling discomfort of ultrsonic teeth cleaning nearly unbearable, really bad when they blasted a cavity, and have become slightly obsessive about anti-tartar oral hygeine, taking great lengths to avoid the procedure. I also submitted to it as a pain treatment once- made it worse. So, instinctively, I say, keep it away from my poor brain, it faces enough challenges as it is. :)

The ostensible treatment doesn't fix anything inside the cell so would need to be repeated periodically over the life of the patient. The vibrational g-forces required to produce cavitation are quite high and we know that boxers and football players develop brain problems with repeated jarring hits to the head.

And what happened to the 25% of mice that failed? Not enough power = no effect, too much power = cell damage? Also. rapid localized heat buildup can, in effect, "fry" the cell. I suspect that there is a fairly thin line between presumed therapudic effect and cell disruption. That is, after all, a major application today:

http://www1.lsbu.ac.uk/water/enztech/ultrasonic.html

"The treatment of microbial cells in suspension with inaudible ultrasound (greater than about 18 kHz) results in their inactivation and disruption. Ultrasonication utilises the rapid sinusoidal movement of a probe within the liquid. It is characterised by high frequency (18 kHz - 1 MHz), small displacements (less than about 50 mm), moderate velocities (a few m s-1), steep transverse velocity gradients (up to 4,000 s-1) and very high acceleration (up to about 80,000 g). Ultrasonication produces cavitation phenomena when acoustic power inputs are sufficiently high to allow the multiple production of microbubbles at nucleation sites in the fluid. The bubbles grow during the rarefying phase of the sound wave, then are collapsed during the compression phase. On collapse, a violent shock wave passes through the medium. The whole process of gas bubble nucleation, growth and collapse due to the action of intense sound waves is called cavitation. The collapse of the bubbles converts sonic energy into mechanical energy in the form of shock waves equivalent to several thousand atmospheres (300 MPa) pressure. This energy imparts motions to parts of cells which disintegrate when their kinetic energy content exceeds the wall strength. An additional factor which increases cell breakage is the microstreaming (very high velocity gradients causing shear stress) which occur near radially vibrating bubbles of gas caused by the ultrasound.

Much of the energy absorbed by cell suspensions is converted to heat so effective cooling is essential. The amount of protein released by sonication has been shown to follow Equation 2.9. The constant (k) is independent of cell concentrations up to high levels and approximately proportional to the input acoustic power above the threshold power necessary for cavitation. Disintegration is independent of the sonication frequency except insofar as the cavitation threshold frequency depends on the frequency.

Equipment for the large-scale continuous use of ultrasonics has been available for many years and is widely used by the chemical industry but has not yet found extensive use in enzyme production. Reasons for this may be the conformational lability of some (perhaps most) enzymes to sonication and the damage that they may realise though oxidation by the free radicals, singlet oxygen and hydrogen peroxide that may be concomitantly produced. Use of radical scavengers (e.g. N2O) have been shown to reduce this inactivation. As with most cell breakage methods, very fine cell debris particles may be produced which can hinder further processing. Sonication remains, however, a popular, useful and simple small-scale method for cell disruption."

Simply blowing away all the amyloids (instead of fixing the cell, like Anavex2-73 does) besides not being "the solution" also exposes the cells to infection. Interesting full article. I have posted an excerpt:

"A new study finds that a key protein implicated in Alzheimer’s may normally protect the brain from infection"

http://www.scientificamerican.com/article/antimicrobial-mechanism-gone-rogue-may-play-role-in-alzheimer-s-disease/

[...]

"The idea that amyloid beta has a positive function in the body could potentially change how scientists approach potential treatments. Instead of attempting to completely eliminate the protein, “we might want to think about just dialing it down,” Tanzi says. Moreover, Moir adds, the drugs in trials now are for the most part designed to reduce inflammation by targeting pathways in the adaptive immune system. But if amyloid production and deposition are innate immune responses, then targeting pathways of innate immunity or the microbes themselves may be the way to go.

They do not expect convincing the scientific community of this to be easy. “This is really going to cause a lot of unrest in the field,” Tanzi says. “Any new revolutionary discovery is first ridiculed, then violently opposed, and finally taken to be self-evident. We’re ready for the ridicule and the violent opposition, and we think we have enough data so that we can look forward to self-evident.” "