US public company NeuralStem reports some data from autopsy findings in their ALS clinical trial. It was Phase 1 safety trial, assessing fetal neural stem cells, transplanted into spinal cord of ALS patients. The results of trial were published here and here. To me, this is the most transparent trial, that I ever seen in highly regulated settings. What I mean by transparency is clinical data reporting (2 publications, multiple press-releases and massive mass media coverage), public sharing of patient informed consent form, sharing details of cell product characterization. Today’s release indicates survival of transplanted stem cells in 6 autopsied patients:
“We can also report that we found evidence of cell survival in all of the patients who came to autopsy, including our first patient who died 30 months after transplantation.
Five of these patients had discontinued all immune suppression medications for 57 – 638 days prior to death, but showed the stem cell DNA content in the range of 0.67% – 5.4% of total DNA in some spots of cord treated with the stem cells There was no correlation of DNA content to survival period without immune suppression medication. These data, therefore, suggest that long-term immuno suppression of patients is not required for long-term survival of our cells, which points towards the feasibility of needing only transient immune suppression in future ALS trials,” Dr. Johe concluded.
This is a good news! We’re waiting for publication of more detailed report. It will be especially interesting to look at immunohistochemistry data, cell proliferation assessment, immune reaction and possible migration of donor’s cells. At this point, the company can’t link cell survival with clinical benefit, because Phase 1 was not design to assess the efficacy. Even if, we look at raw clinical data from this phase, we can see very mixed and unclear results.
Long-term persistence of allogeneic fetal neural cells in patient’s brain was showed before in Parkinson’s disease, Huntington’s disease trials and ALS clinical studies, but it was not demonstrated for spinal cord. The cell product is quite unique, more sophisticated and well characterized. It was derived from spinal cord of just one fetus.
The results of autopsies, give us a hint that engraftment and persistence of cells could be superior mechanism of therapeutic action. Paracrine and trophic effects can not be excluded, but could be less significant. The company just received NIH grant (which will cover almost entire cost of the next phase) and is waiting for FDA approval to proceed for Phase 2.
Disclaimer: I don’t have any financial conflicts of interest and don’t own a stock of the company mentioned in this post.