November 17, 2015

Microbubbles and Ultrasound: An Innovative, Non-Invasive Technique to Penetrate the Blood-Brain Barrier and Treat Brain Tumors, Alzheimer’s, and Parkinson’s.

Last week, a headline on the site Independent.ie caught my attention: “New hope for Alzheimer's, Parkinson's and brain cancer patients as scientists break blood-brain barrier.”

This new hope was reported by neuroscientists at Sunnybrook Health Sciences Centre in Toronto, Canada, where they have developed an innovative, non-invasive technique to deliver medication more effectively to previously “unreachable” parts of the brain. How? By managing to more successfully cross the “blood-brain barrier” (BBB).

Occasional visitors to this blog will have heard me talk about the BBB before. It’s the ingenious, protective “blockade” designed to prevent harmful or toxic substances from entering the brain via the bloodstream. It’s there for an excellent reason: the BBB keeps us safe.

But the BBB also presents a formidable obstacle to introducing potentially beneficial chemical therapies to the brain. I’ve mentioned this BBB “complication” in reference to prescription drugs and also to dietary supplements, like the curcumin I take.

In the case of curcumin, manufacturers found that the introduction of pepperine – the active ingredient in black pepper – enhanced their curcumin product’s “bioavailabilty,” i.e., its ability to successfully cross the BBB and “work its magic.”

The most common medication for Parkinson's disease is carbidopa levodopa. The levodopa is the key ingredient because it helps replace the dopamine destroyed by Parkinson's. Carbidopa enables more levodopa to cross the BBB, and reduces some of levodopa's side effects, like nausea.

What Exactly IS the BBB?
Before we take a look at this new technique, it might help to understand more clearly just what the BBB really is. Here’s the way the November 8, 2015 press release from Sunnybrook Health Sciences Centre described it:
Each person has a protective blood barrier lining the blood vessels in the brain to restrict the passage of large toxic substances from the bloodstream into the brain. 
You can imagine the barrier acting like saran wrap around the small blood vessels. In most areas of the body, there is no saran wrap and whatever is in the bloodstream can get into the various tissues of the body, such as muscle, etc. 
In the brain, all of the blood vessels have this “saran wrap” around them that only allows very select molecules to get through.
That “saran wrap” does an excellent job blocking potentially valuable substances which are created to treat brain diseases like tumors, Alzheimer’s, and Parkinson’s. For example, estimates suggest that certain chemotherapies designed to treat brain tumors have only a 20% chance of reaching those parts of the brain they need to reach… all because of the properly operating BBB.

If doctors could “manipulate” the BBB for therapeutic purposes, a variety of positive cascading outcomes might follow:
  • Medication could be delivered more directly and more accurately (to the tumor, for instance).
  • More successful targeting would improve treatment and require less medication (like chemotherapy).
  • Less medication would reduce damage to healthy tissue and create fewer side effects.
  • Fewer side effects would enhance quality of life.
So, How Did These Scientists Break Through the BBB?
The Canadian neuroscientists combined two elements – microscopic bubbles and high-tech, MRI-guided ultrasound – to open up the BBB to allow the therapy to arrive essentially full strength at exactly the right part of the brain. Here’s how the Sunnybrook press release explains the process:
The research team infused a chemotherapy drug, then tiny, microscopic bubbles, into the bloodstream of a patient with a malignant brain tumour. The microbubbles are smaller than red blood cells and pass harmlessly through the circulation. The researchers then used state-of-the-art MRI-guided focused low-intensity ultrasound (sound waves) to target blood vessels in the BBB area near the tumour. 
The waves repeatedly compress and expand the microbubbles, causing them to vibrate and loosen tight junctions of the cells comprising the BBB. Once the barrier was opened, the chemotherapy flowed through and deposited into the targeted regions.
Other Therapeutic Uses
This technology is brand new, still very much in development, and has so far been used only on “research participants” prior to surgery for brain tumors. 

While other therapeutic applications remain untested, scientists believe the technique of “opening up the BBB” for direct and accurate targeting of therapies with microbubbles and ultrasound will have potential uses down the road for neurological conditions like Alzheimer’s, Parkinson’s, and some psychiatric conditions.


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