Promise of cell replacement for PD – depends on who you are reading….
Science aside, opinions on cell replacement therapy (and future research funding) may be influenced by the wording of the the trial results. One can look at tissue transplants as a “failure” because after 14-16 years there was evidence of cell damage or as a “success “ because there was also evidence that transplanted neurons survived for up to 14 years and trial participants did “ experience some long time relief of their PD symptoms.”

What is highlighted in the articles – the pathology or the relief of symptoms, even if limited ? Whose opinions are we reading? Are there any possible conflicts of interest noted by the researchers? who should receive the limited funding?

For example Published in April 2008 Nature Medicine were a series of communications on the Lewy body-like pathology found in the brains of trial participants.

Written by Jeffrey H Kordower, Yaping Chu, Robert A Hauser, Thomas B Freeman & C Warren Olanow
Title: “Lewy body–like pathology in long-term embryonic nigral transplants in Parkinson’s disease"

In the same issue of Nature medicine, Ole Isacson, and his team report that
"Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years." (Title)

Another letter by Olle Lindval et al stated “,,available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.”

Another report by Isacson’s team from Aug 2009 Journal of Neurology:
. 2009 Aug;256 Suppl 3:310-6.
Title: Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients.
Cooper O, Astradsson A, Hallett P, Robertson H, Mendez I, Isacson O.
“Abstract :Postmortem analyses from clinical neural transplantation trials of several subjects with Parkinson's disease revealed surviving grafted dopaminergic neurons after more than a decade. A subset of these subjects displayed isolated dopaminergic neurons within the grafts that contained Lewy body-like structures. In this review, we discuss why this isolated cell damage is unlikely to affect the overall graft function and how we can use these observations to help us to understand age-related neurodegeneration and refine our future cell replacement therapies.”

Is the glass half empty or half full?

I think it's half full, and beleive that most PDers, especially those who have suffered for more than a few years with this disease to where it is really beginning to impact their life, would gladly take a "decade or more" of not just stopped progression (ie, getting no worse) but actual IMPROVEMENT, even reducing meds or eliminating them entirely. You cannot dispute the testimony of Mr. Turner or the guy featured on the PBS special, they were BETTER, and stayed improved for many years. The PBS guy actually died of something completely unreated to PD, if I remember correctly, and that was 14, 15 years after his implant surgery.

What med or combination thereof can do this now? None. Not even close. As that article said about the incredible discovery that MS is pretty much cured by a stent-type surgery in the brain vein (as I call it), we should similarly expect a "long and hard fight" from those who stand the lose the trillion-dollar PD market if a non-Rx treatment or solution is offered up. We already know how corrupt the scientific research and publication world can be, and I don't see that improving if the PD cash cow is threatened. Good for those who question and look for hidden agendas.

I am not looking at this as a glass half full or empty. A young onset person diagnosed with Parkinsonism at 20 will not feel fortunatel to be granted 10 more years of symptom free life. If he wants more than ten years, he will be forced to live with Parkinsonism symptoms until he is totally debilitated before trying the implant. If he or she is a devout Christian he (she) would be forced to have the death of a child on their conscience to gain 10 years of a life knowing their will end sooner than a person without PD.

I stand firm in the belief the science and God work hand in hand. God gave several persons the calling to find a cure. Understanding the disease is the only way to find a cure.

Vicky

Vicky, my understanding of the implants I referenced in my post is based upon the fact that they were autologous, meaning, derived from the person himself. This is what Excell center in Germany does, and other places as well, although some in South America use umbilical cord stem cells...

I am interested in docs taking cells out of my body, culturing them, and then putting them back in somewhere, brain, liver, kidney, wherever they are needed, depending on the condition. The work done with fetal cells has resulted in tumours which they have as yet not been able to control....and there are a host of other problems with using fetal cells (see my prior post about fetal cells, nothing political, just science based), and I think most of the work being done now is either with IPS cells (cultured cells from one's body that are reverted back to their stem cell state) or actual stem cells taken from your bone marrow. THAT is the work I am watching, and I think is most promising.

Now, having said that, yes, if you get hit with PD when you are 25, ten years doesn't really help you the same as if you are dx'd when you are 70...but then again, I still think most folks would take stem cells and the improvement they can bring over meds over the same amount of time. Also, it may be that you could get multilple implants, one every 10-15 years or so, depending on the severity/impairment. I still think it beats the meds we currently have, and think folks should have the choice of that procedure if they are willing to undertake the risk, since it's still surgery, at least now.

This article is vague but the signatures on it are well known. So we need to know which cells they are referring to and why they mentioned the sham surgery design.

This confuses me - what trials - are they including fetal cell studies overseas? i only know of one in the U.S. and since when did freezing, falling, and gait dysfunction become nondopaminergic? Did i miss something?

I understand that there are many nondopaminergic factors but i wouldn't have picked these symptoms as examples.

In addition, disability in advanced patients primarily results from features such as gait dysfunction, freezing, falling, and dementia, which are likely due to nondopaminergic pathology. These features are not adequately controlled with dopaminergic therapies and are thus unlikely to respond to dopaminergic grafts.

IMHO
paula

Dear Lurking,

I have also undergone risky surgery (DBS) which enabled me to cut way back on my meds. Perhaps this will also need to be repeated as it is less effective over time also. I appreciate having that choice.

I have no problem with adult stem cell research. If you read Paula's mentioned post with a link to her prior post on pluripotent stem cells, you may be happy to know I was one of the patients with mutations in my Parkin gene who donated some of my skin to create pluripotent stem cells. Research in this area requires cooperation between genetics and stem cell research. Because I have 2 mutations, my children all have at least one Parkin mutation and possibly two. One is a college professor and one is a lawyer. I also have a third son who is a truck driver. I love them all and will sacrifice all I have to ensure they do not suffer as I have with this illness.

I would much rather see the science be done slow and methodically (the stem cells from my sample will be exposed to suspected toxins believed to cause PD, pointing to a cure,) and solving the mystery of Parkinson's etiology as well as other brain disorders, than to continue wasting money on thesis' that may or may not work.

If you choose to have the surgery, I wish you nothing more than an improved life quality and happiness.

Sincerely,
Vicky

different people - different viewpoints. i see what everyone is saying and i prefer to read them all. It prevents speculation. This article leaves me [anyway] wondering about the direction these names [who mean different things to different people] are going.

paula

Paula wrote:
“… since when did freezing, falling, and gait dysfunction become nondopaminergic? Did i miss something?

I understand that there are many nondopaminergic factors but i wouldn't have picked these symptoms as examples.”

(Quote from article: Dopaminergic Transplantation for Parkinson’s Disease: Current Status and Future Prospects
Annals of Neurology [2009] 66 (5) : 591-596 (Olanow CW, Kordower JH, Lang AE,
Obeso JA.)
“In addition, disability in advanced patients primarily results from features such as gait dysfunction, freezing, falling, and dementia, which are likely due to nondopaminergic pathology. These features are not adequately controlled with dopaminergic therapies and are thus unlikely to respond to dopaminergic grafts.”

I’ve been wondering about this too. Aren’t freezing, falling, and gait dysfunction motor symptoms?
PDF has a good web page listing many more PD symptoms . They categorize them as Primary Motor, Secondary Motor, and Non-motor. Motor symptoms include resting tremor, rigidity, Bradykinesia (Slow Movement) and Postural Instability (Impaired Balance and Coordination) See:
http://www.pdf.org/en/symptoms

Under this organization, it seems freezing, gait and balance problems fall in the Motor category. But are they also nondopaminergic symptoms? Maybe we’ve been incorrectly thinking of non-motor and nondopaminergic as synonymous? Can anyone clarify?

Excerpt from article cited above:
“The failure of dopaminergic cell-based therapies to achieve efficacy in double blind clinical trials, the development of unanticipated and occasionally disabling side effects, evidence that implanted cells themselves can develop the pathological changes of PD, and the likelihood that these treatments will not address the nondopaminergic features of the disease do not bode well for the near-term future of cell-based therapies as a clinically meaningful treatment for the majority of patients with PD. For the present, it would seem that greater opportunities for more effective therapies in PD would derive from better understanding of the etiology and pathogenesis of the disease and the development of neuroprotective therapies that might slow or stop disease progression."

Yes, it would be great to have a treatment that addresses motor and non-motor, nondopaminergic and dopaminergic symptons AND provides neuroprotection and someday we will have such a treatment. Until then, those of us suffering with plain, old motor problems, and side-effects from years of taking levodopa would welcome a treatment that could provide a number of years (10 or more) of relief, and a more normal life, even if it is not yet the new “gold standard.” And I don’t mean reformulations of levodopa.

I agree with Paula its important to know where the scientists see PD research heading, especially if it is going in a new direction and better yet for patient input to be included on where its headed.