I read a very interesting article on the PBS(Public Broadcasting Station) website this morning about how red blood cells could be infused with different medications and even DNA to distribute within the body. In fact the better news is that this medication would be in the body for approximately 120 days sometimes less due to the damage done to the red blood cell in the process. Thanks to researchers at MIT those of us with autoimmune diseases and allergies, the article mentions this being 8% of the population, that were hopeless before might now have a glimmer of hope in the future say biology professors Harvey Lodish and Hidde Ploegh who are collaborating on this project. The pair say that essentially whatever your organic chemist can come up with can be placed in these red blood cells. This may revolutionize the way certain medications are delivered forever.
The idea of using red blood cells to deliver medication has in fact been around for decades, however this medical miracle has just been put into practice now. The main benefit of using red blood cells is their subtle way of sneaking past the bodies defenses when it’s attacking itself allowing medication to be delivered in a promising new way. Normally enzymes called cytochrome P450s, which are tasked with neutralizing foreign molecules would eliminate medications coming in as well, well not when hidden well inside of a red blood cell and they’d also be able to completely avoid the immune system. This is the reason this new method of introducing medication to an autoimmune or allergy patient may be so very crucial to modern day medicine. However this isn’t the first time medication had been introduced via red blood cells, it was done as early as the 1970’s , said Dr. Vladimir Muzykantov of the University of Pennsylvania, when researchers experimented with using enzyme-loaded red blood cells to treat Gaucher disease. Through these studies we saw that simply injecting the missing enzyme isn’t always effective: the immune system, unused to the molecule, sometimes reflexively unleashes the same type of attack that peanut proteins prompt during allergic reactions.
“The researchers soaked red blood cells in an enzyme solution so salty that the cells burst open and swallowed the enzyme. Thus fortified, the red blood cells raised enzyme levels in cell cultures from Gaucher patients more effectively than the enzyme alone. But though the treatment seemed poised to take off, it was quickly dealt a blow when the HIV/AIDS epidemic hit in the 1980s. Suddenly, any treatment involving blood transfusions seemed too risky to pursue.”
“A few labs, including Dr. Muzykantov’s, kept pursuing red blood cell therapies. In the last decade or so, advances in medical technology have revived the possibility of using red blood cells to deliver drugs. Muzykantov, for example, has developed techniques to stick an anticoagulant to the outside of red blood cells and hitch a ride to dangerous blood clots, helping to break them down. The encapsulation method explored in the 1970s is alive and well, too, thanks in part to better screening for HIV-infected blood: several European companies have already started clinical trials.”
I am glad to hear that some researchers are still pursuing their work from over 40 years ago and striving to make progress in this relatively new and successful approach to delivering drugs. Unlike white blood cells carrying medications which have been caught by the immune system for example the cancer drug macrophage looks like an invading bacterium to the body after being encapsulated in a plastic shell.
As the author of the PBS article mentions neither of these articles is perfect since as I mentioned earlier you’re damaging the cell by hiding medication within so they often don’t last their full 120 day lifespan. This is where Ploegh and Lodish’s research comes into play!
“It works like this: Ploegh, Lodish, and their team begin by fiddling with the red blood cell genome so one of the cell’s surface proteins contain an additional five amino acids. Those added amino acids, known as a tag, attract specific a bacterial enzyme called sortase, which kicks off one specific amino acid in the tag, glycine, and latches on in its place. The beauty of sortase is it can then be exchanged for just about any other molecule you want the cell to carry, provided it has a glycine available: small drug molecules, other proteins, even pieces of DNA. “You’re essentially limited only by what your friend the organic chemist can come up with,” Ploegh says. (Normally, there’s a risk of cancer associated with treatments using genetically-modified cells, but since red blood cells have jettisoned their DNA by the time they’re mature, there is no risk in this case, Ploegh says.)”
According to Ploegh and Lodish the attached compounds will continue to work throughout one’s body so long as the red blood cells are circulating. They also say since the cells distribute the DNA before they’ve matured there is no risk of cancer involved. This may in fact be a defense against biological weapons as it could soak up dangerous molecules for up to four months! In contrast to the few weeks an anti-toxin will buy you this is a major improvement in the world of medicine! Ploegh and his colleagues call this method “sortagging” after the tag and its bacterial enzyme which will traverse all 150 miles of the circulatory system.
Pleogh is careful to stress that these applications are “fairly fanciful and very much in the distance,” but both he and Hubbell contend that using modified red blood cells to create a less excitable immune system could one day be a realistic possibility.
Whether or not Ploegh and Lodish’s method will someday be a most practical way to do that isn’t clear yet. For one thing, it requires modifying cells’ DNA, which, Hubbell points out, “is a lot easier to do in the laboratory than it is to turn it into a pharmaceutical process.” That’s why Hubbell’s work currently focuses on designing antibodies that will bind with red blood cells inside the body—no genetic engineering or transfusion needed. In practice, “sortagging” would be, says Batrakova, the pharmacy professor, “basically personalized medicine,” which is challenging to implement on a grand scale. That’s not to say it’s impractical, Hubbell says. “One would just have to find the applications that warrant the complexity.”
So sortagging would essentially be personalized medicine you’d just have to find a case that warrants such drastic measures. Essentially people whose only hope is a clinical trial of a new drug, people like me who are terminally ill and have no other options. The study still remains to be seen in humans as at the moment it’s being done in mice. Ultimately, though, Muzykantov thinks all these approaches are complementary, not mutually exclusive. Batrakova agrees: “I think that the more approaches we have, the better.”
Thank you to Eleanor Nelson for writing this thought provoking article on the PBS website and thank you to my mother the amazing RN who pointed this out to me. I continue to be amazed and hopeful that recent advances in medicine will someday save my life or at least get me into remission so I can go out and seek a real job! Thank you for reading and I hope if you have any sort of autoimmune disease or if you suffer from allergies that this article has raised your spirits and that you know have more hope for the future.