Testing, testing, 1,2,3
Some of the heartiest laughs we’ve had as a family have been after my father got sick with MS. I’m not sure why we laugh; it seems that we appreciate the little things in life so much more, like the faces Dad makes while telling a story about how the dog ate his slice of pizza, or the moments we spend reminiscing around the dinner table.
My Dad is a statistic, one that has affected our family personally; MS is among the autoimmune diseases that are collectively ranked the third cause of morbidity in the United States. This hits home, and consequently, I am always on the lookout for new research on MS.
Recently, I saw a press release out of Northwestern entitled,
“Breakthrough nanoparticle halts multiple sclerosis”
The headline prompted me to track down the corresponding journal article, and someone who could translate it into “grad student language”.
I had the chance to sit down with Northwestern University researcher Dr. Stephen Miller, a corresponding author on a paper published last month in Nature Biotechnology. The paper itself is extremely technical, even for an immunologist in training such as myself!
I’d like to share the knowledge that Dr. Miller imparted to me with you, on this, my very first blog post!
I asked Dr. Miller to tell me about his work on this paper. He explained that his lab has been working for 30 years to understand why the immune system mistakenly destroys its own cells and tissues in autoimmune diseases.
In MS, this is a problem; the immune system attacks the insulation surrounding nerve cells in the brain, spinal cord, and eye. This impairs electrical signals, resulting in numbness, paralysis, or even blindness. Current therapies for autoimmune diseases suppress the entire immune system, making patients more susceptible to other infections and to increased risk of developing cancers.
In 1985, Dr. Miller’s lab discovered that the immune system in a mouse model of MS ignored dead cells, and set out to understand the mechanisms by which these dead cells evaded detection. Over time, they learned that this system could be used as a disease therapy, by attaching a cocktail of proteins making up the insulation surrounding nerve cells to the dead cells, and injecting them into mice.
This particular study has now completed the phase I safety trial in MS patients, and will need funding to proceed to a phase II trial.
Based on these successes, and the high cost and complexity of carrying out the therapy using dead cells, the Miller lab turned to inert nanoparticles, in hopes that they might also evade detection by the immune system gone rogue in MS patients.
The paper published last month shows, in short, that indeed, the nanoparticles attached to the proteins that are attacked in MS are able to deliver their cargo to a receptor on the surface of immune cells, which virtually resets the immune system so that it no longer destroys the insulation surrounding nerve cells.
Don’t worry, Dr. Miller and his colleagues went to great lengths to show that the substance used to make these nanoparticles is safe to inject into people – the substance (called PLG) is the same that is already approved for biodegradable sutures. Of course, the study will enter safety trials before the technology is approved for therapy.
After two and a half years of work on this study, Dr. Miller told me that he hopes to partner with a biotechnology company, or perhaps create one, in order to translate these findings into an effective therapy for people like my father.
As you can imagine, I was particularly excited about this paper, as well as the opportunity to speak with Dr. Miller about his work on MS. The nanotechnology may also be effective against other autoimmune diseases, such as psoriasis and type I diabetes by simply changing the protein attached to the nanoparticles.
Warning, this is technical: I’ve included part of a figure from the paper, showing that treatment of mice during remission from MS (at day 18 following induction of disease) with PLG nanoparticles decorated with a myelin protein (the insulation surrounding nerve cells, labeled PLP in the figure), shown as closed triangles, can protect the mice from undergoing disease relapse, while PLG particles decorated with an egg protein (OVA, shown as open triangles) cannot.
In addition, Dr. Miller has given me permission to link this WGN video, which further explains the study.
More to come!