Cancer Drug to Treat Glue Ear in Kids??!

I read with astound that a class of cancer drugs known as VEGF Inhibitors (ie, Avastin and Erbitux) used to treat colorectal, lung, breast, and kidney cancers can also be used to potentially treat a type of chronic ear infection known as glue ear... at least in theory and in mice. Glue ear is when an individual suffers from repetitive ear infections or upper respiratory infections to the point where the fluid in the ear turns into a maple syrup consistency. It's thick, sticky and tough to get rid of with standard antibiotic medications. Standard treatment to address glue ear is placement of ear tubes to allow ventilation and drainage of the ear as well as antibiotic/steroid ear drops.

British researchers using the mouse model have determined that an underlying hypoxic (low oxygen) environment in the middle ear leads to glue ear and that by mediating aniogenesis (blood vessel growth) by regulating VEGF receptors (Vascular Endothelial Growth Factor), may prevent glue ear from occurring by addressing the root cause (hypoxic environment). VEGF inhibitors are typically monoclonal antibodies that prevent new blood vessels from forming via blocking VEGF receptors.

Given a vial of anti-VEGF costs on upwards of $10,000 versus not even $100 for an ear tube, the economics of this potential treatment just does not make sense at this time. Even if the costs were more comparative, I'm not sure most people will go for a treatment normally used to treat cancer to address a benign condition.

However, to be fair, this class of cancer medicine has been repurposed to treat other benign conditions including age-related macular degeneration (AMD) and diabetic retinopathy, so who knows?

It's also been considered for use to treat severe nosebleeds due to HHT (Osler-Weber-Rendu).

Maybe someday in the near future after further research, not only will we have antibiotic ear drops, but also anti-VEGF ear drops!!!


Reference:
HIF–VEGF Pathways Are Critical for Chronic Otitis Media in Junbo and Jeff Mouse Mutants. PLoS Genet 7(10): e1002336. doi:10.1371/journal.pgen.1002336

Gluing Cut Blood Vessels Together

Gluing blood vessels together, just like gluing a cut garden hose together, does not seem like a great idea at first, but Stanford researchers just might have figured out how to do this safely and effectively.

Over the past century and still currently used today is to hand-sew the cut ends of the blood vessel together using stitches. This method of reattaching blood vessels is time-consuming and tedious, especially when the blood vessels are tiny.

In this new glue method which is FIVE times faster, a special substance is injected into the cut blood vessel on both ends called a poloxamer. This substance has the unique property of becoming an elastic solid when heated above body temperature which than turns into a biodegradable liquid that dissolves away when cooled.

In a nutshell, the steps are as follows:

1. The poloxamer is inserted into the blood vessel where is solidifies using a halogen lamp thereby keeping the lumen open.


2. The cut edges of the blood vessel are precisely reapproximated and "glued" together using dermabond, a substance currently used to "glue" together cut skin.


3. The blood vessel is allowed to cool down by taking away the halogen lamp and the poloxamer contained within the blood vessel melts and dissolves away.

So far, this procedure has only been done in animals, but since all of the components of this technique has already been FDA-approved for human use for other purposes, if proven to work, can rapidly be adopted for microvascular surgery in humans.

Reference:
Vascular anastomosis using controlled phase transitions in poloxamer gels. Nature Medicine (2011) doi:10.1038/nm.2424

Novel Treatment for Glue Ear?

Glue ear is the layman's term for thick mucoid effusion of the middle ear, usually due to chronic ear infections.

The fluid itself is like maple syrup and usually treated with ear tube placement followed by suctioning as much of the fluid out as possible. However, given there is always some residual present, antibiotic ear drops with steroids is often prescribed.

Unfortunately, these patients are at higher risk of requiring repeated sets of tubes after the body spits them out.

Why?

Because of a phenomenon called biofilms... Think of it as teflon armour made of slime for infections. You can put antibiotics and steroids on it, but they kind of just slip off. Such biofilms make infections nearly 1000 times LESS susceptible to medications. In order to truly eradicate the biofilm (and underlying "hidden" infection), you either have to "scrape" it off which is not possible in the middle ear or use very high concentrations of antibiotics... much greater than that obtained using oral or IV antibiotics.

Though ear drops containing high concentrations of antibiotics are possible, the drops tend to come out of the ear just as easily as they go in preventing prolonged and enduring contact.

That's were the recent innovation comes in...

Scientists in England have developed a biodegradable antibiotic "pellet" that can be inserted into the middle ear during surgery where it will slowly release high concentrations of antibiotics to target any infections present (active or inactive) over 3 weeks continuously. Furthermore, the pellet contains N-acetylcysteine which effectively breaks apart the biofilm.

In essence, this pellet is like an armour-piercing bullet.

Of course, it is not available in the US yet... nor is it FDA approved.

Read more about this here.