On SIRT1 and nanoparticles
Recently, some exciting M.S. research results were forwarded to me by friends.
In May 2013, results of an M.S. study was reported in Inside Stanford Medicine, a publication by the Stanford University School of Medicine. The study itself, entitled "Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain” was published in the journal Nature Cell Biology (Nat Cell Biol. 2013 Jun;15(6):614-24).
Usually, the protein SIRT1 is considered to be beneficial for health. However, in M.S. and other demyelinating diseases, inactivating it seems to show that it then stimulates the production of neural stem cells that make the myelin sheaths.
The work suggests that SIRT1 may normally limit the production of myelinating cells after childhood development and that it has to be inactivated to again allow the production of these cells.
These researchers think that eventually it may be possible to induce the brains of patients with M.S to heal themselves by blocking SIRT1. Of course, lots more research is needed.
Another trial, "Antigen-specific tolerance by autologous myelin peptide–coupled cells: a phase 1 trial in multiple sclerosis" (Sci. Transl. Med. 5, 188ra75 (2013) suggests that reintroducing a patients' white blood cells back into the body, like a Trojan-horse, secretly carrying modified myelin antigens, results in the immune cells starting to recognize myelin as harmless. It only had nine participants, which is “too few to be called a study” according to our primary doctor, but it does suggest an exciting new line of research.
And nanoparticles, which are cheaper and more readily available than a patient’s white blood cells, are proving to be just as effective as delivery vehicles.
This is good news! I’m really interested in stem cell therapy, and this seems to me to be a way to get it without first entirely knocking out the existing immune system.
So go, go, go!
But researchers still don’t know what causes the disease.
A friend recently forwarded me an article from the Inside Stanford Medicine newsletter. It seems that a small, recent study showed that there may be two different schemas for MS.
So MSers’ responsiveness to the available therapies, and interferons in particular, might depend on which pattern of MS we have.
This totally fits with my experience: my disease has never seemed to be halted by the meds, or even overpowered temporarily by steroids. Even chemotherapy didn’t seem to have any effect.
And when my neurologist told me that in his opinion I had transitioned to secondary-progressive, I thought “Well, duh?! I’ve been thinking that for several years now!”
In fact, this study may be suggesting that I’ve been progressing since day one, that although my diagnosis was Relapsing-Remitting Multiple Sclerosis (RRMS), it may actually have been some progressive form all along.
In truth, once getting this diagnosis 20 years ago, I suspected that doctors often gave the diagnosis as RRMS then they could prescribe one of the first-line drugs for MS that are only approved for this type.
MS medication is so expensive and has required self-administered, regular shots, sometimes as often as every day.
This study seems to confirm for me that giving myself the regular, sometimes painful, shots did nothing to slow the progression of my disease.
And that’s the mystery for all of us: there is yet no way to measure the effects of any of our medicines. I have no way to measure this, so I only have my gut feeling.
My doctor agreed that the latest medication I was administering faithfully had obviously not impeded my progression, so we agreed that I should stop.
The silver lining is “Yay, no more shots!”
On the other hand, “Whoa, no more shots. Of any kind.”
He explained to me that prevailing theory at the moment is that MSers who transition from RR to SP eventually reach a plateau and that we can hope that I’ve already reached it.
He did arrange for me to try a new oral drug for MS, A——-, which helps some of the affected walk more confidently. I’ve been taking it for two months now but have experienced no change.
If the results are replicated by other labs and larger studies, MSers may someday be able to take a blood test at diagnosis to see which type they have.
It’s another small piece of the puzzle.
- Goldman, Bruce (2010). Two kinds of multiple sclerosis, two different responses to beta-interferon, study shows. Inside Stanford Medicine, Mar. 28, 2010.
- Also, see the study results published in Nature Medicine:
I personally think the only reason the doctors differentiate between
“types” of M.S. is to give the patient an idea of what is appropriate
to expect. But because of that, there are drugs that are only approved
for one “type” of M.S. so if a doctor wants you to try one you must
be classified as that type. And it really is such an individual, unique
disease: tell J. not to let the label dictate what she is or isn’t
This is a description from an MS Society booklet called “Managing
Progressive MS” that you can download for free at http://www.nationalmssociety.org/download.aspx?id=314
“Progressive MS manifests itself differently in everyone. Whether
your MS is “secondary-progressive” which followed a period of
“relapsing-remitting” MS or “primary-progressive” meaning it has been slowly
progressive from the beginning, it is important to realize that “progressive”
does not necessarily mean severe disability. But it does mean that there are
few or no relapses, and few or no recovery or remission periods when major
With Tysabri (what you called “the chemo”), tell J. not to worry
about the “multifocal leukoencephalopathy” (PML) at this point.
It has been reported in only a few cases and always with people who were
currently taking other immunosuppressants as well. The National Library
of Medicine reports that “there is not enough information to tell whether
using it alone also increases this risk” and that is because it hasn’t
The Multiple Sclerosis Quarterly Review, published by the United
Spinal Association and the Consortium of Multiple Sclerosis Centers, reports
that there have recently been reports of liver dysfunction and two cases of
malignant melanoma associated with its use. But it also reminds us that although there continue
to be safety concerns, it is still “the most effective FDA-approved drug
for treating” M.S. Tell her to have
her liver enzymes checked with regular blood tests.
I got Tysabri once when it was first approved and was tired but fine (I always
think that except for this “pesky M.S.” our immune systems are
superstars). But the following Monday it had been pulled from the market
because of the initial PML discoveries. In the meantime I had an MRI and
there was little change so my doctor decided not to resume it for me when it
came back on the market. The bottom line is that there are both risks and
benefits to all drugs and also that chemotherapies tend to have less side
effects in recent times.It has really
helped some people.
Also, I can totally relate to being too proud to ask for help. When OH
was in the hospital and I was spiraling downhill, I was finally able to ask my
mom for help. She was so pleased to be able to do something,
so I think it might help J. to ask if she knows how helpless you feel and don’t
know unless she tells you what you can do that she would really
appreciate. My mom washed, folded and put away laundry, washed dishes,
scrubbed the shower and cooked meals for my freezer for months.
Learning to ask for help is one of the lessons this disease is trying to teach