Focused Ultrasound

In March 2015, a story broke in the Alzheimer's community about an ultrasound treatment which restored memory functions.  A year later, the story regularly circulates and I get tagged with it by finds pretty frequently.  I totally understand the excitement around this announcement.  If it turns out to be correct, then we may have a winner here.  However, let's take a moment to break the story down a bit.

The story headlines are often quite sensationalistic such as the one above which screams "New Alzheimer's Treatment Fully Restores Memory Functions."  However, upon reading the text of the article, on quickly learns that the treatment is being performed on mice.  Lines of genetically engineered mice have been created to mimic Alzheimer's symptoms so that researchers can test their hypothesis against the mice instead of against humans.  Mice do not naturally develop Alzheimer's or Alzheimer's-like symptoms.

Why are mice used?  Mice breed prolifically which makes many readily available for those who need to study a specific line of mice.  Mice age quickly, allowing symptoms to be seen in one year instead of waiting decades for symptoms to be seen in humans.  They are small and easily cared for.  Mice carry fewer ethical or practical burdens for study or experimentation than larger animals or animals which are more closely related to humans.

What we've seen with numerous studies before is that something which looks promising in mice has not yet been found to work in humans.  Diseases are very complex.  With Alzheimer's we are not yet sure what causes the disease beyond a shadow of a doubt.  Is it the presence of Amyloid Beta and Tau tangles or is Alzheimer's itself several different concurrent diseases?  When we're not 100% sure, then the line of mice which are designed to exhibit a particular (set of) symptom(s) may be designed off of a completely false assumption or designed to present a biologically simplified version of the disease as noted in how mice are used to study Type 2 diabetes.  In cancer research, it has been found that using mouse models had less than an 8% successful translation to humans.  What this means is that less than 8% of the research using mice ended up being applicable to humans.  When there is success, it can be huge for those people who have the disease in question.  In 2010, the European Union debated the use of mice in studying human disease.  They acknowledged it is problematic but does offer hope for success.  However, at least one scientist has since raised the concern that part of the high failure rate is associated to the high rate that these industrialized lines of mice are compromised from the start.  They're fat and that makes them prone to disease and of limited use to research.

So, the mice are flawed and the pre-clinical work has a high likelihood of failing when human subjects are engaged.  What about the treatment?

The scientists claim to have used focused ultrasound to open the blood-brain barrier and stimulate the brain's microglial cells.  Let's break this down a bit more.

Waves of ultrasound energy are directed to a particular area.  In High Intensity Focused Ultrasound, this results in the cells in the area being heated to the point they die but not to the point where the liquids within them boil.  This is an effective treatment for some tumors for example.  This is not what the researchers want to do in the brain.  So, they may be looking at Low Intensity Focused Ultrasound or Transcranial Pulsed Ultrasound.  Both of those are lower energy output which increase cellular activity without killing the cells.  There's hope that the ultrasound use will allow for more medication to cross the blood-brain barrier. 

Microglial cells clear debris and dead neurons from the Central Nervous System.  If the treatment does increase the activity of the microglial cells, they will work to clean out any cell that is dead and they won't just focus on the plaques.  While they may help clean up the dead cells hanging out in the brain, they're not rebuilding the cellular connections.  However, low intensity focused ultrasound does stimulate cell growth.  The concern here is that it is not focused on any one type of cell and ultrasound is very difficult to target effectively.  So, they may end up stimulating the growth of cells which were unintended.

If we look at the source announcement, what we see is very different than what the headlines crow.  The use of focused ultrasound in treating Alzheimer's is just in its infancy.  The research is in a pre-clinical/early stage and is not currently for use with humans.  They are using 2 different lines of mice at two different universities.  The source material states that the researchers are hoping to open the blood-brain barrier to allow for medication to be more easily delivered to the brain.  The source material also states that they hope to stimulate neuron activity.  It does not claim that their mice are regaining memories.  A year later and the research has not been updated.

While I wish them well, I'm not sure that this approach will provide us with a treatment in the long run.


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