(Dr. Eva Feldman, MD, Ph.D,FAAN, FANA)
Russell N. DeJong Professor of Neurology
Director, A. Alfred Taubman Medical Research Institute
Director, Program for Neurology Research and Discovery Univ. of Michigan
Posted: June 18, 2013
On Thursday of last week, Dr. Eva Feldman gave the plenary address at the Canadian Neurological Sciences Federation Annual Congress. During the talk she showed 50 slides detailing the long history of our ALS clinical program, discussing the technological issues with surgery into the spinal cord as well as a myriad of issues involved with neural stem cells. In summarizing the trial data to date, she reiterated that the preliminary data showed that patients with a short disease duration prior to surgery and no bulbar symptoms, can show disease stabilization and/or improvement after intraspinal stem cell transplantation (based upon ALSFRS, FVC, EIM, Spasticity/QOL scales).” These conclusions now include data from the three subjects in the trial who received five unilateral cervical injections each. One of the patients in this cohort who had bulbar symptoms died. Five of the six patients who died during the trial (out of fifteen) had bulbar symptoms and died of ALS 7-to-30 months after surgery; one patient died of unrelated heart problems. The two remaining cervical-only injection patients were reported to be in the “stable or improved” category.
Dr. Feldman did not show the actual data slides that she showed in a talk recently in Romania, but rather summarized those results. She spent considerably more time in this talk, than in Romania, going over the remarkable surgical feat involved in this therapy. While we, at Neuralstem, tend to think of this now as rather routine, it is worth taking a second to appreciate just what we are taking for granted.
We are placing cells directly in the motor neuron pool area of particular segments in the grey matter of the spinal cord. We do this because this is where the motor neurons reside that die in ALS patients, and it is the death of those cells that leads to the atrophy of the muscles which cause the symptoms of the disease. Our cells integrate into the host tissue and nurture and protect the remaining healthy cells, and most likely in patients whose scores increase, nurse some “sick” cells back to better health. It is a remarkable demonstration of the power of cell therapy. But none of it would matter if we couldn’t put the cells in the “right” location, that is directly into these motor neuron pools in specific spinal segments. As our surgeon Dr. Nick Boulis once said to me early on, “None of your science is any good if I can’t hit the spot.” To give us a feel for that, Dr. Feldman showed a slide with a (2005) dime (face side up). Since 1946 the face on the dime is that of Franklin D Roosevelt. I urge all of you take one out and look at it. Hitting the “spot” in each segment of the spinal cord for this therapy is the equivalent of hitting the chin on President Roosevelt’s face on the dime.
Dr. Feldman also talked about our upcoming FDA approved trial and noted that there will now be three centers involved; Emory, Michigan and Massachusetts General. I need to amend this to point out that, while this is the plan, we have not yet formalized an agreement. We will announce it when we do. Finally, it was noted that the FDA has approved a trial designed to considerably increase both the dose escalation throughout the trial and the pace of the treatments. In our Phase I ALS trial, we were restricted to transplanting no more than one patient every four weeks. The Phase II trial has no artificially-imposed time structure. Instead, this will be determined by our Independent Safety Monitoring Board and sites as they get comfortable with the increased dosage and number of injections. We need to see the same pristine safety profile we saw in the Phase I trial for both the surgery and the cells, but it is hoped that this new timing flexibility will allow us to finish the trial in less than half the time it took to complete the first trial.
There is a great deal of interest in the data from this trial, as well there should be. We expect peer-reviewed publication this fall will afford the next detailed look at it, as well as Dr. Feldman’s presentation at American Neurological Association Annual Meeting in New Orleans in October, where she is the President.
Dr. Feldman spoke of how long the journey has been to find a potential treatment for ALS, and how arduous the process of demonstrating that our cells could be that treatment. I can tell you: It took a good three years to complete our Phase I ALS trial at a single center, with just one surgeon treating each patient. Preclinical studies took just as long before that. Along the way, Dr. Feldman was steadfast in her belief that we would persevere. Whenever something finally went right or got approved, I would receive a simple short email...”progress!” was all it ever said.
Now we hope to complete our Phase II trial in just 18 months at multiple world-class centers. We have demonstrated that the delivery of the cells is safe and robust. We have demonstrated that the cells themselves are safe and that they survive long term in the patients. We have demonstrated that we can provide stabilization and/or improvement for nonbulbar, early- stage patients. We have demonstrated, through the approved Phase II protocol of more cells and more patients at a faster pace, that the FDA is getting comfortable with this ground breaking technology and totally new approach to treating this terrible disease. “Progress” indeed.