[Tupelo3]

Voluntary move made after audit finds weaknesses in results of tests on rats.

A pioneering trial by Living Cell Technologies of transplanting pig cells into the brains of humans with Parkinson's disease has been temporarily halted at Auckland City Hospital because of deficiencies detected in one of the earlier trials of the treatment in animals.

http://www.nzherald.co.nz/lifestyle/...ectid=11180336

[pegleg]

Tupelo

Thanks for this. This trial design (or I suppose I should say its prediction ) was very similar to the Spheramine trials in which I partipated 13 years ago.

The efficacy was to measure Endpoints after transplanting retinal cells (dopamine-producing) from a donor eye, one eye able to provide enough cells for as many as 10,000 patients with Parkinson's . The transplants were not cross- matched in any way and no immunosuppressant meds were required. The delivery of cells to the hippocampal or caudate area was done stereotaxically. ( not sure of this spelling).

I was one of the original six to participate in the open label safety phase. After four years, the phase I participants maintained a nearly 50% improvement of individual baseline symptoms. The investigating physicians were singing Spheramine's praises at a professional conference. in Helsenki. A few weeks later the trial was suddenly halted while phase II results were finalized. The word of mouth reports were that Spheramine trial results from phase II failed miserably to meet its Endpoints. How could that be???

The published results did not make the scene until nearly two years later! I'd like to know how that was acceptable. In my opinion, the explanation as to how they could be singing the trial's praises while reporting that endpoint results were not met could come a few weeks later. This was the same trial but consisting of a larger sampling of participants (6 inthe phase I safety phase, approximately 74 participants in the phase II randomized multi-facility double- blind design).

Both trials used a cell delivery system requiring porcine or pig cells that then encapsulated the cells to be injected via stereotaxic surgery. And remember this important safety factor - NO immunosuppressant drugs we're needed or used which often causes all types of rejection problems.

I would like for a good reputable statistician to compare the trial results and design Tulpedo has provided the above link for to the Spheramine trial. Pig cells vs human donor retinal pigmented epithelial (RPE) cells seems to be the major difference, in my nonprofessional opinion.

We, as people with Parkinson's or other interested individuals (caregivers, friends, family scientists and Parkinson's clinicians) should be asking lots of questions. Both these trials did not carry the stigma most " living cell" transplant trials carry - the belief, ethics, and safety or dangers of using cells such as embryonic cell transplants have carried in the past.

Forgot to include Spheramine link to report
http://www.ncbi.nlm.nih.gov/m/pubmed/18394567/

[Tupelo3]

Peggy, first let me start out by saying regardless of the trial outcome, you are to be commended for participating in this study, along with everything else you do. Without human volunteers for research studies, it is literally impossible for us to succeed in finding new interventional and symptomatic treatments.

Although the Spheramine trial was before my "PD" time (and I'm not that familiar with it) I believe the issues were very different than the Living Cell Technologies (LCT) pig cell transplantation study I posted. The LCT human trial was halted because of faulty record keeping in the pre-clinical animal studies. When the oversite committee tried to replicate and validate the results from the same data, they realized they had serious research control and data collection issues. What was similar to your study, though, was the inexcusable delay of several years before reporting the issue and data. One thought I have had in this regard is forming a patient led group to review the timeliness of all researchers in posting their trial results. We would stick to PD research. If they are tardy, or don't post at all, they get penalized. We lobby foundation to stop funding them in the future, and we don't participate in their studies. That will get them to either cooperate, or retire.

With regard to the little I know about your Spheramine trial, I guess the classic, and boring, initial response would be the power of the placebo effect in your open label Phase I. I recently read a study reviewing hundreds of PD trials. The placebo effect is VERY strong and long lasting. However, a more interesting response relates to your saying that you didn't have any effect until about the 9th month. The endpoint in the Phase II was only 12 months. So, maybe they just didn't wait long enough to find a positive result. It certainly would seem logical to think that it would take a long time for this type of intervention to start working. A final thought would be just the differences in people. Its possible that the transplant would work with some people, or some forms of PD, and not others. That would sort of negate finding a positive result in a larger study which may not be true in the smaller 6 patient phase I. Remember, only certain types of individuals will volunteer, like you did. Maybe all 6 of you were very homogenous in many traits and that was somehow related to the success of your trial.

Just some thoughts.

Gary

[soccertese]

bottom line it's ridiculous that these dinky little companies are doing this cutting edge research and not big pharma but i'm glad someone is doing it.

seems like every gene/cell transplant trial involving surgery except for fetal transplants have had great phase I results and failed in phase II. Along with the strong placebo affect in pd patients willing to participate in these trials, the bungee jumper type personality, i've seen speculation that since they are all open label, and the primary researcher is involved, AND there is money involved, the scoring is sometimes a little biased, data is thrown out, participants washed out.

this includes the AMGEN GDNF infusion trials, titan pharmaceuticals spheramine, neurologix's gaba gene implant, ceregene's neurotrophic genes, then there was the recent oral trial of that small naturally derived product in england that failed phase2.

then there is that OXFORD something or other 3 gene for producing dopamine implant that seems stuck.

as an aside, i participated in a trial of a new agonist called sumanirole, seemed to work quite well, compared it to requip and i initially got requip, dosed up to the right dose, then later stopped requip and dosed up on sumanirole. my symptoms were very mild so hard to compare symptomatic affect but side affects were less in sumanirole, and i heard that it worked better anecdotally in more advanced patients. study was suddenly cancelled as pfizer bought out pharmacia which made sumanirole. from the following posts, seemed like others thought sumanirole worked well and pfizer buried the drug, where's their incentive to develop a better product? they did do a lot if EKG's during the trial.

http://www.medicalnewstoday.com/opinions/4506/

[dilmar]

Interlude: (comment totally in jest)

From the land who brought bungee jumping to the world here's hoping that a dinky little company (albeit Australian) solves this one!

[soccertese]

Originally Posted by dilmar

Interlude: (comment totally in jest)

From the land who brought bungee jumping to the world here's hoping that a dinky little company (albeit Australian) solves this one!

i hope so too, is that why you moved back to NZ?