[soccertese]

excerpt, he does go into more detail in full opinion piece:
14 AUGUST 2013

Now For The Bad News

The Holy Grail of PD research is to find a disease-modifying therapy. If one could deliver neurotrophic factors to the putamen, for example, and rescue ailing dopamine neurons, it might change the trajectory of the disease. Unfortunately, most recent efforts have ended in failure. Setbacks include Amgen’s negative glial-derived neurotrophic factor (GDNF) infusion trials, Ceregene’s two failed Neurturin gene therapy trials (in 2008 and 2013) and Phytopharm’s 2013 unsuccessful trial of Cogane, an oral medicine designed to stimulate growth factor production. Some scientists like neurosurgeon Steven Gill argue that this neurotrophic strategy may eventually work, when researchers figure out how to deliver the right dose on the right schedule to the correct area of the brain. Others argue the failures have a simpler explanation — there’s nothing left to rescue; that trial patients’ nigrostriatal damage is too advanced to reverse.


This bleak conclusion is suggested in a landmark paper by Jeff Kordower et al., which investigated nigrostriatal pathology in 28 post mortem Parkinsonian brains and compared them with 9 controls. Since the PD patients survived for varying lengths after diagnosis (from 1-27 years), Kordower et al. set out to estimate dopamine loss in the substantia nigra pars compacta and putamen at different stages of the disease.


Using stains for two proteins normally active at dopaminergic terminals—tyrosine hydroxylase (the enzyme that converts tyrosine into L-dopa) and dopamine transporter (a protein that mediates dopamine reuptake) — Kordower et al. searched for dopaminergic damage. The team found plenty. At diagnosis, the substantia nigra pars compacta and dorsal putamen had lost respectively 50-90% and 50% of their functional markers. But as the enclosed figure graphically shows, the news gets much worse. By 4 years post diagnosis, the tyrosine hydroxylase stain in the dorsal putamen was completely gone. The team found an almost identical picture of total loss over 4-5 years in the dopamine transporter stains.

http://www.journalofparkinsonsdiseas...mans_Blog.html

so stem cells and/or fetal transplants for advanced pd'ers? just my layman's take.

[Tupelo3]

[QUOTE=soccertese;1009361]
Others argue the failures have a simpler explanation — there’s nothing left to rescue; that trial patients’ nigrostriatal damage is too advanced to reverse.

QUOTE]

Which all leads back to my earlier posts that the NIH study and other studies may be using patients to far advanced. Its the reason why the study samples must include early stage patients if we are to get some answer as to the efficacy of these growth factor drugs. Even then it may be too late. Basically, these studies may be guaranteeing failure by insisting on a sample of late stage patients.

To quoted from the article you linked:

“Neurotrophic factors will only work if you start super early. If you wait until the formal diagnosis has been made, there's often a lot of destruction, and you can't really hope to reverse that.” British neuropathologist Chris Hawkes says by the time a patient gets a firm diagnosis of PD, “the pathology is far more advanced than you’d think…. And to put it crudely, the brain is well and truly pickled.”

[soccertese]

i just have to wonder if less advanced pd'ers would volunteer knowing that receiving genes, etc. into the brain would likely preclude them from any future trials and of course there is a small risk of brain damage. i'm amazed someone volunteers for these trials in lieu of getting a DBS, thank god there are people willing to volunteer.
wonder if the NIH GDNF trial selection criteria includes a DATSCAN?

the fact that some patients showed improvement 18months after the first ceregene trial i think spurred the 2nd trial which wasn't all that expensive, so why not give it a try? not really trying to debate that trial, just putting myself in the shoes of the researchers and why they did the trial. dam*ed if you do, dam*ed if you don't.

if you listen to the MJFF webcast on that trial, the researcher said they had 2(?) patients die after(?) the first trial and autopsy showed some nerve growth, and he said they hadn't any deaths among the 2nd cohort to check nerve growth and someone from MJFF stepped in and said something like the deaths in the first cohort were not caused by the trial. so i guess they felt that was enough evidence to proceed with 2nd trial?

certainly not trying to create an argument here.

[Tupelo3]

Originally Posted by soccertese

i just have to wonder if less advanced pd'ers would volunteer knowing that receiving genes, etc. into the brain would likely preclude them from any future trials and of course there is a small risk of brain damage.

No doubt its a huge dilemma. However, if the Phase 1 safety studies come out ok (which they basically have been so far) I think you would get volunteers. Especially if the research continues to show that nothing else works on advanced patients. My analysis would be, take the shot when I can as opposed to hoping something comes along down the road, goes through 20 years of research and then becomes available to me when I'm 80.

Just a thought, and I agree with all of your issues.

[soccertese]

https://www.michaeljfox.org/foundati...-trial-results

they throw out the possibility that they can only measure symptomatic relief and not possible neuroprotection. biomarkers again, we need better biomarkers.

the fact that some fetal transplants worked well in the 90's and lasted longer than a few years, at least that's my understanding, makes me wonder why it's just now that new fetal transplant trials are planned in europe.

i tend to think that if some new procedure works well in phase2, we won't have to wait 20 years. imagine if the ceregene or cogane results had been fantastic. i wonder how the FDA would be responding to pressure from the pd community to fast track phase3, etc?

hoping this stem cell therapy gets funded:
http://www.summit4stemcell.org/

Summit4StemCell (S4SC) is a grass roots, volunteer fund raising organization supporting non-embryonic stem cell research conducted by Jeanne Loring Ph.D. and Melissa Houser, M.D. S4SC operates under the nonprofit status of the Parkinson's Association of San Diego (PASD). Summit4StemCell inspired a partnership with PASD, The Scripps Clinic in La Jolla and the Scripps Research Institute in an effort to further the fight against Parkinson's through this promising research.

Summit 4 Stem Cell Mission: To fund non-embryonic stem cell research that will result in a treatment for Parkinson's while inspiring people with the disease to move beyond their physical limitations.

[budgies]

Originally Posted by soccertese

https://www.michaeljfox.org/foundati...-trial-results

they throw out the possibility that they can only measure symptomatic relief and not possible neuroprotection. biomarkers again, we need better biomarkers.

the fact that some fetal transplants worked well in the 90's and lasted longer than a few years, at least that's my understanding, makes me wonder why it's just now that new fetal transplant trials are planned in europe.

i tend to think that if some new procedure works well in phase2, we won't have to wait 20 years. imagine if the ceregene or cogane results had been fantastic. i wonder how the FDA would be responding to pressure from the pd community to fast track phase3, etc?

hoping this stem cell therapy gets funded:
http://www.summit4stemcell.org/

Summit4StemCell (S4SC) is a grass roots, volunteer fund raising organization supporting non-embryonic stem cell research conducted by Jeanne Loring Ph.D. and Melissa Houser, M.D. S4SC operates under the nonprofit status of the Parkinson's Association of San Diego (PASD). Summit4StemCell inspired a partnership with PASD, The Scripps Clinic in La Jolla and the Scripps Research Institute in an effort to further the fight against Parkinson's through this promising research.

Summit 4 Stem Cell Mission: To fund non-embryonic stem cell research that will result in a treatment for Parkinson's while inspiring people with the disease to move beyond their physical limitations.

Not sure if I'm reading this thread correctly, but is this saying that there's no hope of a cure?

[Tupelo3]

Originally Posted by soccertese

[url]i tend to think that if some new procedure works well in phase2, we won't have to wait 20 years. imagine if the ceregene or cogane results had been fantastic. i wonder how the FDA would be responding to pressure from the pd community to fast track phase3, etc?

.

Yeah, I know I was exaggerating. Although, keep in mind, the first human studies on Cere-120 were done in 2006. Even if the last Ceregene study was successful, you would still probably have 3 -4 years to complete Phase III and come to market. Unfortunately, the fact is, Ceregene and Cogane results were not fantastic. However, imagine if they would have been fantastic had the sample group had a early stage subgroup........ We'll never know.

[soccertese]

my entry expressed great hope in cell transplants but i'm not a scientist.
the question for us older pd'ers is what will be the cuttoff age/criteria to get into a clinical trial or get the "cure", when i was diagnosed at 48 i thought cure in 5 years, now i'm nearing 60. just trying to stay healthy so i'll hopefully qualify for something.

[budgies]

Didn't mean my message to be ambiguous, just misunderstood the first posting, in that I thought it meant there was no hope for someone a few years along the line with PD.

Thank you for clarifying it for me.

[soccertese]

Originally Posted by budgies

Didn't mean my message to be ambiguous, just misunderstood the first posting, in that I thought it meant there was no hope for someone a few years along the line with PD.

Thank you for clarifying it for me.

you also have to keep in mind that baby boomers, at least in the US, will have huge political clout and might be able to demand that these treatments be given to older patients. as will the medical companies.

and to be blunt, not something that i waste a lot of time worrying about but sure should motivate me to be active in supporting effective pd research while i still can.