Nurr1


#1
Reading more and more has made me conclude that neurotrophic factors are not the solution for PD. I hope I am wrong and that the cogane study will prove otherwise. However, I found this amazingly interesting article about why neurotrophic factors don't seem to work; but even more interesting, what should be done to make them work. This might well be the biggest breakthrough in PD yet:

http://www.aan.com/elibrary/neurologytoday/?event=home.showArticle&id=ovid.com:/bib/ovftdb/00132985-201301170-00005

#2
to quote

"said that scientists involved with trophic factors had [u]for years[/u] known that GDNF did not work in the alpha-synuclein models and “ignored this fact and used other models. But we all knew it was a problem.”

so the f******* b******** took the f******** money for their f********* useless experiments knowing all the time that it was total b***s****!!!!!!!!!!

to say i am peeved is an understatement - these f******* should be injected with 100mg of mtpt and see how they f******* like it!

i am totally furious - the people we depend on most have let us down.

#3
I don't know where the truth lies but i prefer to hold on to this while awaiting the outcome of the GDNF trial just starting.


From: Report from the University of Bristol

Post-mortem analysis of the brain of a phase I GDNF trial participant at the University of Bristol in the UK, revealed re-growth of nerve fibres in the putamen area of the brain. The findings are reported in the July issue of Nature Medicine.

The patient died of a heart attack. Professor Love, who examined his brain “found that dopamine-containing nerve fibres had sprouted back in the putamen. He said: “This is the first neuropathological evidence that infusion of GDNF in humans causes sprouting of dopamine fibres, in association with a reduction in the severity of Parkinson’s Disease."

#4
...on the other hand....

#5
Turnip, you are right. There are many strange things in PD research.

http://www.prnewswire.com/news-releases/amarantus-bioscience-reports-statistical-significance-achieved-for-manf-striatal-reinnervation-in-neurorestoration-animal-model-of-parkinsons-disease-189649741.html

A recent study that shows MANF is better than GDNF. But again on a 6-OHDA rat model. The FDA should be a bit more strict here and force them to these tests on an alpha-synuclein rat model. Why would a company even do this ? I think they test on these kinds of rats, so they get funding from MJFF. Even if it doesn't work for PD, they can probably push their neurotrophic factors the cure people that had strokes and seizures.

Another strange thing is the cogane study. I read on neurotalk forum that people had to take cogane pills in combination with some coconut oil vessel (not coconut but something with ketones in it) in order to avoid stomach problems. I seriously have no clue why on earth would they do this. There is research going on to verify whether ketones can improve symptoms in neurodegenerative diseases. So why would you give patients a vessel like that ? It could also explains why in Alzheimer's clinical phase II the placebo group also had an increase in the score.

Anyway, let's wait what the cogane study says this month.

#6
mister x
i was going to apologise for my outburst, but the very idea of researchers wasting government and charity money on research that they KNOW is crap is so sickeningly abhorrent that i don't think i will. I remain disgusted.
So now we know that bigpharm runs the russian mafia close for 'evil organisation of the year', that researchers only care for where the next grant comes from and charities (present company excepted yeah right) are a bunch of spineless wonders... pass the green tea and say a prayer to st anthony for the return of lost dopamine neurons.

grrrrrrr

#7
Turnip

No need to apologise. You are right. I have had similar outburst in the past. Especially with the GM1 ganglioside study. This was something invented in the 80's. We are now 2013 and still a clinical phase III needs to be started. And even if this trial would give positive results, GM1 ganglioside will never be sold anyway because big pharma's want a pill form. So the MJFF is trying to make such a pill and as a consequence of that they are starting with such pills in preclinical trials on rodents. Worst part, they don't even know if this is going to work at all. When I found out about this, I had an outburst too.

On the other hand, there are other things that are being funded that will make a difference. For example, I know my father has a mutation in the GBA gene that gave him almost 7 times more probability of getting PD. This is one of the most common forms of familial PD. MJFF is funding Amicus therapeuticals. They found a chaperone that increases the expression of an enzyme that is lacking in people with mutation in the GBA gene: http://www.amicusrx.com/programs.aspx. Tests on animals show this chaperone is very promising for PD linked to this specific gene.

There are also other studies that seem very promising. The biggest concern in PD is a-synuclein. Many treatments are in development to target a-synuclein. You have the Affiris vaccin; the Belgian company Remynd; ... and several others whose name I forgot. There is also LMTX for Alzheimer, which also shows preclinical efficacy for PD. Without the charity money we wouldn't have got this close to a cure. I honestly believe in 10 years PD will not be the feared disease it is at the moment. If you look at what is present in the pipeline and what is known about the disease, it is all more promising than ever. Nurr1 is another extremely promising lead. So don't worry. In the end, money is well spent. The only drawback is that we need 5-10 years before the current pipeline is available for PD patients.

So it isn't all that bad. By the way ... don't be too early with throwing away the neurotrophic factors:

https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=1069

:wink:

#8
Oh, and if CDNF would work, than also BDNF would work as apparently it has the same mechanism: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085896/

And Cogane increased BDNF ... anyway, we will soon know more about this.