• It is a tale Told by an idiot, full of sound and fury, Signifying nothing.

Posted: September 28th, 2011

“….it is a tale

Told by an idiot, full of sound and fury,

Signifying nothing.”

- Macbeth

Shakespeare’s bitter, frustrated, yet eloquent rant on life…who among us has not felt like this at times? There are so many things we don’t know, so much of life that indeed seems random and meaningless. Yet also so much that is wonderment and joy. The Jewish new year begins this week, and as part of the ritual we ask God to write our names in the book of life for the upcoming year.

(As an aside I have always thought it rather odd but fortunate that we confess our sins of the past year and ask for atonement later, on Yom Kippur, conveniently after we have been written into the book.)

And in that way that annual religious rituals seem to inspire, we think about life and what it means. But the question is more than an intellectual exercise for those suffering from fatal diseases, like ALS patients and their loved ones.

We released the data on the first twelve patients in our ALS trial at Emory University this week. Dr. Eva Feldman, the principle investigator in the trial presented the data at the ANA meeting in San Diego. CNN also carried a story that included an interview with one of our patients, a patient who is experiencing a quantitative reversal of many of the symptoms of the disease. Two of the 12 patients in the trial have died; one from a pre existing heart condition, the other from late stage ALS. Of the surviving patients, 8 out of the 10 have seen the rate of decline of their lower extremity muscle control and strength either slow down, level off, or get better. Since we have only placed cells in the lower back area, this is the only area we might expect or hope to see improvement. That we do is very encouraging, but it is only that. 12 patients is too small a sample to draw any conclusions from, and there is no control group, no “placebo” group to make sure that any improvement we do see, is “real”. The trial was designed, as the FDA requires of all first trials, as a test of the safety and feasibility of our transplanting our cells directly into the spinal cord. Not to test whether the cells can help. We measure those things, but in a way, we are really just “practicing” for the later trials where such measurements will be the primary end points of the trials.

This is how real science is done. Additionally, this is how our system for discovering new therapies “protects” us from unnecessary risk and harm.

The surgical route of administration we need to get our cells where they need to be requires the world’s first intra spinal injections. There were indeed many serious unknowns involved in the surgery, as well as the use of our cells. Sober minds concluded that there was serious risk. I know all the arguments, and I know they are right. I was reminded recently that our own surgeon, Nick Boulis, (who developed the device we use and the surgery itself) told us we were crazy the first time we approached him with the idea of multiple injections directly into the grey matter of the spinal cord. After our experience with the first 12 patients, we are seriously considering up to forty (40) injections ultimately as a therapy. Half the patients in our first trial received 5 injections each, and half 10 injections each. Serious risks require serious caution.

But for those whose prayers to be entered into the book of life for yet another year are desperate pleas, not grateful musings, our system must seem, as Macbeth curses, all sound and fury, signifying nothing. What good is protection if you protect people to death?

I have no answers, no way to reconcile the innate contradictions involved in developing novel, risky approaches for incurable diseases. Everyone involved in this trial, from the patients and their families to the doctors and nurses at Emory is doing all they can to bring the hope of a better, longer life to ALS patients, whether or not it can benefit them or their own loved ones. As I have told the many patients and families I have been privileged to meet or hear from since we began this effort; we are working as hard and as fast as we can, and as hard and fast as they will let us. If you have read patient #11’s story, you can not help but be moved; as we are all moved, by all of their stories, regardless of the ending.

Yes, twelve patients is far too small a sample to draw any conclusions from; and yes the lack of a placebo group also requires extra caution when assessing the data from the patients. But the patients are now 6 to 20 months out; and each month we get more information on how they are doing; and we are able to assess a little better, the safety of our cells and our surgery; and to measure also any possible slow down in the loss of, or even an improvement in, function. And the take home message so far, is the more we look, the more encouraged we are.

We believe in the weeks ahead (there is a great deal of data for them to review), that the FDA will approve the next groups in the trial and we will start transplanting cells into the upper regions of the spinal cord. It is with these injections that we hope to be able to improve the breathing function of patients, to improve their quality of life, and to extend those precious lives. Again, this trial will be designed primarily to test the safety of such injections, but again these are real patients, getting the real cells, and we hope to see encouraging results in other measurements too. And we will work as hard and as fast as we can to make all the sound and fury signify much more than nothing.

La shana tova