The stem cell clinic trial being run by Asterias Biotherapeutics for spinal cord injury (SCI) reported (via CIRM) some preliminary very good news as it is so far seems safe and will be expanded to involve more patients. In the next phase, reportedly “Asterias is now looking to enroll 5-8 patients for this 20 million cell phase.” You can also read the company’s PR on this development here.
CIRM’s report by Kevin McCormack on this advance also included a window into the personal story of a young patient, Jake Javier, who is a participant in the trial:
“For people like Jake Javier this news is not about numbers or data, it’s personal. Earlier this summer Jake broke his neck at a pool party, celebrating graduating from high school. It left him paralyzed from the chest down with extremely limited use of his arms and hands. On July 7th Jake was enrolled in the Asterias trial, and had ten million cells transplanted into his neck.”
Jake is some kind of hero! Here’s more info from Asterias’ PR:
“The SCiStar study is an ongoing Phase 1/2a clinical trial funded in part by a $14.3 million grant from the California Institute for Regenerative Medicine (CIRM) and is designed to evaluate the safety and efficacy of escalating doses of AST-OPC1 in newly injured patients with sensory and motor complete cervical spinal cord injury (SCI), as well as newly injured patients with sensory incomplete SCI. These patients are commonly referred to as AIS-A and AIS-B patients, respectively. The results of the ongoing trial continue to support a positive safety profile for AST-OPC1. There have been no serious or unexpected adverse events related to AST-OPC1, the administration procedure or the accompanying short course of low-dose immunosuppression in any of the patients treated with AST-OPC1, including five patients in an earlier Phase 1 trial with neurologically complete thoracic SCI.”
The hope is that as this CIRM-supported trial proceeds, there will be continuing evidence of safety as well as indications of efficacy. Way to go CIRM and Asterias.
For more on this development see David Jensen’s interesting piece over at California Stem Cell Report.
“ESCs and IPSCs have potential that some other types just don’t from my view”
@Paul, could you please explain the advantages of ESCs and IPSCs to us? I just read/thought MSCs are the most encouraging type of stem cells for the future? Thank you
@Richie,
Every type of stem cell is going to have +’s and -‘s.
For pluripotent cells, some of the challenges are (1) tumorigenicity (hopefully largely resolved by differentiation and purification methods, along with rigorous genomic and epigenetic validation) and (2) potential immunogenicity for ESC (addressed with transient immunosuppression if needed, yet still an issue) but likely not needed for IPSC.
The pluses include the power of pluripotency to in theory make any individual cell type you want if you can develop a protocol for that differentiation, great scalability (you can grow an almost infinite # of cells) and the unique ability to form actual complex tissues including both in vivo and potentially in the long run in the lab which could then be taken advantage of (e.g. via organoids) to transplant fully developed mini-organs back into the patients.
For adult stem cells, the challenges include very limited potency and inability to make complex tissues, and limited growth potential (although practically speaking you can still expand them pretty well before senescence). There are notable cell types like those of the CNS that simply cannot be made by MSCs.
The pluses of MSCs include very low tumorigenic potential, no need for immunosuppression if used in an allogeneic fashion, ease of obtaining (at least in the case of liposuction, less so with marrow aspirate that is a more involved procedure, but still not too bad), they can in the right context form a few specific tissues like cartilage very well (although one wonders– do they really engraft in any significant rate?), and they can secrete helpful growth/other factors in some cases.
There are probably other +’s and -‘s for each too.
In my view pursuing both adult and pluripotent makes the most sense and for both we should expect top notch data & FDA approval (in the US) before marketing to the general public.
Paul,, couldnyou fix these typos above?
As this study is based on ESCs
any bit but of good
scope of information
Thank you.
Fixed
@Paul, we all hope this succeeds but, with all do respect, I think you are a little too glowing in your commentary on this article considering the small number of patients so far (only 8) and no indication of any sign of efficacy. Safety in adult stem cells has be demonstrated time and time again in clinical trials so that it has become routine. As this study is based on ESCs I suppose that may be a reason for your enthusiasm? The CIRM has nothing to show for all the taxpayer money it has spent so far and it can be expected that they would hype any bit of good news but one would expect you to be more subdued given the lack of progress using ESCs and the limited scope of information these data supply, BTW, the term “embryonic” was not mentioned in either the article or your commentary for some reason.
Very true WST
Hi WST,
Yeah this is an ESC-based trial and perhaps I could have mentioned that in the article. I’m very enthusiastic about all kinds of stem cells, but ESCs and IPSCs have potential that some other types just don’t from my view. Conversely, adult stem cells have some unique properties too.
In my article I mentioned risks in this trial and it’s clear we don’t know the outcome ahead of time.
CIRM isn’t perfect, but they have done a great deal of good including in concrete ways with clinical trials and I believe to say they have “nothing to show” is a huge exaggeration.
I’m curious–what adult stem cell clinical trials do you think are the most exciting right now?
Paul
@Paul,
I can point to two adult stem cell trials that have had exciting results, one autologous and one allogeneic. The first is from Cytori using autologous adipose derived regenerative cells to treat hand dysfunction caused by scleroderma, an autoimmune disease. Cytori is currently in an FDA Phase III trial in the U.S. based upon this open label 12 patient study that had spectacular results for a disease that has no treatment: http://www.ncbi.nlm.nih.gov/pubmed/26350489 This is a small indication but the likelihood of approval seems very strong even if the company still will likely need more dilution to get to the finish line.
The trial that gets me most excited is the ischemic stroke trial by Athersys using allogeneic bone marrow derived MAPCs. Although the 90 day Phase II results needed post-hoc analysis to show efficacy, the one year results in this placebo controlled, double blinded trial met the same endpoint – with statistical significance (called “Excellent Outcome”) – that lead to the approval of tPA, 20 years ago. Stroke is a blockbuster indication with a tremendous drain on patients, their families and the health care system. You can read my most recent thoughts about the Athersys stroke program here: http://seekingalpha.com/article/3968415-stem-cell-company-athersys-firing-cylinders-2016 The mechanism of action of this stroke therapy is very well understood and documented and I hope to put an in depth report on the science next week in conjunction with the formal announcement of the commencement of the Japanese stroke trial that will get under way very shortly.
One common theme between these two trials is that the primary mechanism of action involves regulating an overreacting immune system with secondary benefits of angiogenesis (and neurogenesis for stroke) even if the cells don’t engraft. In the case of scleroderma it is chronic inflammation, in the case of stroke it is acute inflammation that does much of the damage.
Thanks, WST.
Seems moderately encouraging. It’s good to see them working w/FDA rather than what the clinics are doing, but I need to learn more about these studies and I’m not sure I still entirely am sold on the indirect immune mechanisms here.
Is this the Athersys trial: https://clinicaltrials.gov/ct2/show/NCT01436487 ? Have they published their data yet? I don’t see it on the clinicaltrials website.
I’ll be very curious to see more data as these proceed. Do you own shares in these biotechs?