Stem Cell Treatment for RA?

Stem Cells

A reader of this blog recently sent me information about a clinical trial involving stem cells as a treatment for rheumatoid arthritis. This prompted me to investigate further.

The American National Institutes of Health has a great descriptive website on stem cells. Stem cells are of interest to researchers since they are able to grow into a variety of different types of cells. They are proposed to be used for cell therapy – cells injected into a patient to impact a process, and regenerative therapy – cells used to regrow or repair damaged tissue. They are theorized to have great potential but that potential has been sought without much success for many years.

There is also a controversy with stem cells having to do with the harvesting of stem cells from embryonic tissue. This harvesting is typically done in vitro meaning that embryos are fertilized and grown in a lab. For those who believe life begins at conception, such harvesting is repugnant. The other type of stem cell harvesting is from adult tissue. Adult harvested stem cells can come from a variety of tissues.

The clinical trial in question is from a company called TiGenix which is a European cell therapy company based in Belgium. They only use adult stem cells harvested from fat or adipose tissue. They claim that their stem cells are less likely to result in immune system reactions resulting in rejection of the cells by the patient. Their stem cell Cx611 was used in a Phase II clinical trial to investigate safety and efficacy for rheumatoid arthritis.  One interesting aspect of this particular clinical trial is that they used patients with “refractory” RA – patients who failed to respond to biologic treatments. The patients receiving the stem cell treatment displayed lower disease activity than those receiving a placebo and safety data was positive. Here is a link to the press release and a link to a detailed presentation about the company’s foray into stem cell research for autoimmune diseases. The stem cells are theorized to impact the biological processes involved with RA induced inflammation and tissue damage. In summarizing the clinical trial, they stated,

“These results are remarkable, as they constitute the first ever signal of clinical activity of a cell therapy in RA. Moreover, this was achieved in the probably most refractory RA patient population ever evaluated in clinical studies.”

Check out this recent blog post from Diana at My RA Diary for a more detailed explanation of stem cell research and RA. In her post, she does an excellent job of outlining the potential of stem cells as a treatment. She cites research and posts some nice videos and diagrams.

It is exciting that researchers are investigating stem cell therapy as a potential treatment for RA. I suspect that we are years away from knowing if it will become a reality. But the Phase II clinical trial conducted in Europe is a promising step in the right direction.

Creative Commons Photo Credit: http://commons.wikimedia.org/wiki/File:Human_embryonic_stem_cells_only_A.png

Brush Those Teeth-Periodontal Disease and RA

Several years ago after an 8 year hiatus, I finally made a visit to my dentist. The hygienist and dentist noted that my gums were red and tender – I had periodontal disease. They used a probe to measure the depth of the pockets between the gums and teeth. There were quite a few pockets that were deeper than desired and it was recommended that I get a “deep cleaning” and then move to a cleaning every 3 months. The deep cleaning required lidocaine shots to numb the nerves since the cleaning tools would probe deep. Realizing that there must be inflammation involved, I started speculating about a possible connection with RA.

Like RA, periodontal disease is an inflammatory condition that can include gum inflammation and eventually damage to tissue and tooth loss. The National Institute of Dental and Cranofacial Research indicate that it is thought to be caused by opportunistic bacterial infections in the mouth. A recent review of studies by researchers in Australia found relationships between periodontal disease and inflammatory blood markers like ESR, C-reactive protein, and interleukin 1 which are all implicated in RA. Associations between periodontal disease and joint destruction from RA have been found (see this study). Some researchers noted connections between the biochemical processes of RA and periodontal disease. A study published in the Annuals of the Rheumatic Diseases in Europe showed that a common blood marker for RA, anti-citrullinated antibodies (anti-CCP), is related to periodontal disease. Other researchers demonstrated that the bacteria Porphyromonas gingivalis, which is one of the pathogens involved in periodontal disease, is linked to anti-CCP antibodies. Another group of researchers indicated that people with RA have a significantly higher rate of periodontal disease than control populations. While there are statistical correlations between RA and periodontal disease, it is not proven that periodontal infections are a cause of RA. The link between the two continues to be explored by dental and rheumatology researchers.

Based on these findings, it is important for RA patients take good care of their mouth in order to avoid diseased gums and teeth. If RA-caused joint damage in the fingers and wrist make it difficult to brush and floss, it may be necessary to use some adaptive tools like an electric toothbrush, a floss holder, and water jet systems. I use an elective toothbrush and let the motor do the hard work. I’ve now gotten the periodontal disease under control and my dentist is letting me go back to 6 month cleanings.

Creative Commons photo credit: http://www.flickr.com/photos/ephotion/39301156/

Living within Limitations

Gardening has been a favorite outdoor activity for years. This love of the ground and raising plants began in 6th grade when I dug up a spot in our yard and planted a vegetable garden. Tomatoes grew like weeds and the joy that came with watching and nurturing plants sank deep in my psyche like tap roots.

As a twenty something high school teacher, summers were spent operating a small landscaping business. I had a truck and hired several high school students as laborers. We would plant shrubs and trees, build retaining walls, and haul bulk items like top soil, rock, and mulch. During this phase of life, I also regularly ran 20-30 miles per week and participated in 5Ks periodically. I never felt better!

Every home we lived in over the years would get hours of loving care in terms of landscaping and gardening. Redoing lawns, building greenhouses, planting flowers, edging and mulching planting beds, planting trees and shrubs, and building fences (see photo) were just a part of life.

Thirty years later and living with rheumatoid arthritis has dramatically changed these activities. This fact was recently evident when my wife started edging a planter bed and digging up sod in order to plant new flowers and lay mulch. In the past, I would’ve been in the thick of this kind of work. She began the digging knowing that I couldn’t help. We were delighted when our wonderful neighbor came over and started helping edge and pulling up sod. Instead of just passively standing by watching someone else do the work, I decided to work on bonsai gardening. The kind of work needed to maintain bonsai – pruning, watering, etc. - is doable given the impact of RA on my joints and energy levels. My dwarf Cedar of Lebanon and Western Red Cedar bonsai seem to be doing very well (see photo).

I can no longer dig sod or haul mulch, but I can still get my hands dirty and nurture plants – just on a much smaller scale!

Diagnose Early, Treat Aggressively, Monitor Carefully

My first systemic autoimmune symptom was in 2004 – I was not formally referred to a rheumatologist. Three years later I had ankle surgeries in both ankles which later was attributed to RA. Again, I was not referred to a rheumatologist. In late 2008 I started having additional symptoms that drove me to my primary care physician. He put all the symptom pieces together and immediately sent me to a rheumatologist resulting in a formal diagnosis five years after the first symptoms appeared. After diagnosis, I progressed rather quickly through a series of treatments (that journey continues today but that’s a story for another post). Now I am nowhere near clinical remission and have a severe level of disease activity that caused permanent joint damage and is dramatically impacting my life. I only wish I knew more about RA back in 2004. The good news is that there are some quality resources available that are designed to encourage early diagnosis and aggressive treatment.

One such resource is an online presentation from Dr. Martin Jan Bergman, a rheumatologist from Drexel University. He recently gave an excellent, relatively short, and non-technical presentation in October 2012 titled Rheumatoid Arthritis: Diagnosis, Treatment and Monitoring. The presentation was sponsored by Quest Diagnostics. His presentation is a superb resource for primary care physicians, RA patients, and care givers to better understand the disease and treatment processes.

One key point made by Dr. Bergman is that RA is more serious than most people think and there is a lack of public awareness of this severity. He points out that RA leads to disability, reduced work capacity, and lower quality of life. He strongly asserts that RA is a lethal disease and he shows how the survival rates of patients with high RA disease activity is similar to coronary artery disease and Hodgkin’s lymphoma. RA also brings about an increased risk of heart attacks, strokes, infection, and lymphoma.

Dr. Bergman is emphatic about early and aggressive diagnosis and treatment of RA. His says that his most common referrers are orthopedic surgeons but argues that this is often too late and primary care providers need to be more aware of RA symptoms. He stated that “there’s no such thing as arthritis- it’s a field of study.” He compares the loose use of the term arthritis to getting a diagnosis of a “belly problem” for a heart attack. With over 100 kinds of arthritis, keying in on the exact nature of the symptoms and diagnostic keys is critical to helping the patient. He discusses common diagnostic tests but warns that lab tests are normal in 35% of patients with RA. Common inflammatory tests like ESR and CRP are also normal 40% of time and should never be used to exclude a diagnosis.

Once diagnosed with RA, Dr. Bergman states that it should be treated aggressively. Waiting only results in permanent loss of function and poorer responses to treatment over time. He describes how the ACR/EULAR classification criteria should be used and he states that monitoring the disease using detailed criteria rather than just asking patients how they’re feeling provides a quicker response to treatments. His goal is to get patients as close to “normal” as possible.

Awareness of these issues discussed by Dr. Bergman is critically important for patients’ well-being. I only hope that more physicians will diagnose early, treat aggressively, and monitor carefully. Patients and care givers will find Dr. Bergman’s presentation enlightening.

Creative Commons Photo Credit: http://www.flickr.com/photos/67272961@N03/6123892769/

Can’t Turn a Blind Eye to RA

There are a few people with whom I can be completely open and transparent about the impacts of RA on a regular basis. There are others who are on a “need to know” basis. And then there are some from whom I try to hide my symptoms mostly from fear of being misunderstood, judged, or penalized. Being in a place where treatments are not working and symptoms are significantly impacting daily life and work, it’s much harder to follow this approach.

A while back, someone sent a note to my blog expressing the notion that my approach to writing about RA was too negative and that they had lived with RA for many years and got along just fine. It’s wonderful that this person has this experience. But that has not been my experience nor is it the experience of a large proportion of people with RA. This comment prompted me to go back and reread my posts reflecting on my journey over the past few years. While many posts were about research related to RA, there were personal posts of celebration along with posts describing the realities of symptoms and treatments.

The Rheumatoid Patient Foundation just published a white paper about the results from a patient survey. The results of this survey clearly paint a picture of patients regularly experiencing symptoms that impact daily life in spite of receiving treatment. The collective voice of patients is critical for developing and implementing effective treatments.

The idiom “turn a blind eye” reportedly came from an admiral who refused to withdraw in the heat of battle. Using this approach in medical situations can lead to serious consequences. Read this excellent article from the Center for Bioethics and Human Dignity at Trinity International University on the topic.

I can’t turn a blind eye to my own RA symptoms, its impact on my life, or the impact of RA on millions of sufferers in the world. Therefore, I vow to accurately share my experiences with those around me as it is appropriate and with the online community via this blog. This will be done in as balanced an effort as possible.

Creative Commons Photo Credit: http://www.flickr.com/photos/kubina/138205823/

The Pains of Sleep

While waiting for the next treatment plan to be revealed by my rheumatologist this Friday, the RA beast seems to be running at will. Joint swelling, redness, warmth along with fatigue are at levels rarely experienced during this RA journey. And this means that pain levels have also increased. At one point a few days ago, finger joint pain induced wincing almost to the point of tears making me ready to pull out the “big gun” painkillers. Friends came over to play spades and it was difficult to hold the cards. Besides the regular squaking joints, joints that tend to lay low, rarely speaking that RA is there, are now screaming loudly. Such was the case a few days ago when the elbows were quite conspicuous. Laying down to bed was anticpated in an effort to get some much needed rest. But the pain was too great. Adding insult to injury, knees and ankles joined in the chorus and throbbed incessantly in an effort to gain attention. Rest was not to be had. No amount of tossing or turning helped. I arose out of bed and stumbled back downstairs and turned on the TV. Of course, this was Thursday night and the live coverage of the tragic events in Boston were unfolding. Attention was rivted to the talking heads trying to get the latest scoop until I crashed from exhaustion somewhere around 2:30 a.m.

Sleep with RA can be an elusive goal. While not inspired by RA but likely by his own personal battles, a poem by the famous English writer Samuel Taylor Coleridge captures the “Pains of Sleep” while living with rheumatoid arthritis.

THE PAINS OF SLEEP

by: Samuel Taylor Coleridge (1772-1834)

Ere on my bed my limbs I lay,

It hath not been my use to pray

With moving lips or bended knees;

But silently, by slow degrees,

My spirit I to Love compose,

In humble trust mine eye-lids close,

With reverential resignation

No wish conceived, no thought exprest,

Only a sense of supplication;

A sense o’er all my soul imprest

That I am weak, yet not unblest,

Since in me, round me, every where

Eternal strength and Wisdom are.

 

But yester-night I prayed aloud

In anguish and in agony,

Up-starting from the fiendish crowd

Of shapes and thoughts that tortured me:

A lurid light, a trampling throng,

Sense of intolerable wrong,

And whom I scorned, those only strong!

Thirst of revenge, the powerless will

Still baffled, and yet burning still!

Desire with loathing strangely mixed

On wild or hateful objects fixed.

Fantastic passions! maddening brawl!

And shame and terror over all!

Deeds to be hid which were not hid,

Which all confused I could not know

Whether I suffered, or I did:

For all seemed guilt, remorse or woe,

My own or others still the same

Life-stifling fear, soul-stifling shame.

 

So two nights passed: the night’s dismay

Saddened and stunned the coming day.

Sleep, the wide blessing, seemed to me

Distemper’s worst calamity.

The third night, when my own loud scream

Had waked me from the fiendish dream,

O’ercome with sufferings strange and wild,

I wept as I had been a child;

And having thus by tears subdued

My anguish to a milder mood,

Such punishments, I said, were due

To natures deepliest stained with sin,–

For aye entempesting anew

The unfathomable hell within,

The horror of their deeds to view,

To know and loathe, yet wish and do!

Such griefs with such men well agree,

But wherefore, wherefore fall on me?

To be loved is all I need,

And whom I love, I love indeed.

Learn More about Drug Development – Take a Free Online Course

There are many choices of drugs when treating RA including numerous DMARDS and biologicals. Most of the currently used RA drugs are relatively new being developed and marketed in the past few years. In an earlier post, I documented that there are dozens of new RA drugs in the development pipeline. Do you wonder where all these new drugs for RA come from? Who develops them? How are they proven to work? What’s the difference between small and large molecule drugs? What are biosimilars? How are new drugs approved for use? How are they marketed? Who pays for the development?

If you want to learn more about these topics, I invite you to join me by taking a short online course from the University of California San Diego called

Drug Discovery, Development & Commercialization

The instructors are Williams S. Ettouati and Joseph D. Ma who are professors of pharmacy at UC San Diego.

This course is what is called a MOOC which stands for Massive Open Online Course.  Massive – Many people from a variety of backgrounds will be in the course, sometimes thousands. There are already over 12,000 people registered for this course! Open – It’s open to anyone and they are free. Online – All of the course activities and information are totally online. These courses are more about connecting and collaborating rather than taking a passive traditional course. MOOCs are rapidly becoming a popular way to take a course from a leading university taught by well known experts in the field. Check out this video and resource if you want to know more about MOOCs. This course is delivered through Coursera which is a leading provider of MOOCs by universities all over the world.

Join me if you want to learn more about this topic which is closely related to RA drugs. This particular course starts April 19 and is 9 weeks long. You’ll probably spend a couple of hours a week reading material and interacting with students. Let me know by sending me an email if you plan to take the course and I’ll look for you online. You can register through the Coursea website.

MOOC image By Andybulle [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0)%5D, via Wikimedia Commons