I haven't seen a reference to it on this site. Does anyone know if this has been discussed?
When I fist came across this, I was very excited, thought about exploring a 'buy group' like what was done with Nilotinib, but then because I have PD, I forgot to pursue it (ha,) but was reviewing bookmarks today and rediscovered it.
"... mean reduction of free serum alpha-synuclein levels of up to 97 percent after a single dose, which were statistically significant (p < 0.0001), and confirmed after two additional monthly doses."
"Prothena's phase 1b multiple ascending dose study represents the first report of an antibody targeting alpha-synuclein in patients with Parkinson's disease and showed that PRX002—also known as RG7935—was able to reduce serum levels of the protein by up to 97% with a single dose."
MBA, Perhaps what's more important than what you are missing, is what the prospective trial-drug is missing. It still seems to fall well short of offering any concrete solutions for those of us upon whom the suspect toxic 'a-syn' process has already taken a significant toll. Once better diagnostics are finally able to detect PD in its earlier stages, the referred PRX002/RG7935 antibody may eventually prove useful as a tool to slow its progression. As it's still "investigational", however, its efficacy in that regard - as well as the precise role that a-syn dysfunction plays in the death of DA neurons - has yet to be established.
Wrong. For starters, halting or even slowing progression is a huge win for anyone with PD regardless of stage. As far as the role of alpha synuclein, you can cast all the doubt you like, but it's a good bet to be the cause of the problem: directorsblog.nih.gov/2013/...
I don't understand your post because it sounds, unless I'm misinterpreting, like you and the link re saying a-synuclean is the problem since the Prothena trial cleared this protein??
PB, Seems you're having a problem distinguishing between an already existing therapy capable of "halting or slowing progression" (which still exists only in one's imagination), and this antibody currently at the center of a prospective "investigational" therapy that "aims to slow the progress of neurodegeneration". A therapy that "aims" to do something, and a therapy that actually DOES what it 'aims' to do are considerably different things. I hope you'll let us know as soon as a "good bet" that a-syn is the "cause of the problem" (together with an ample collection of hopeful adjectives thrown into the study description) succeeds in actually "halting or slowing" your PD.
Once again, the point of my initial (and subsequent) reply fails to compute: The proposed therapy is still "investigational" - "the precise role that a-syn dysfunction plays in the death of DA neurons has yet to be established". Your emotional need to breathlessly declare PRX002/RG7935 (prematurely) capable of "halting or even slowing progression" of Parkinson's based on a "good bet" is the daft sort of 'reasoning' that is tough for people to take seriously.
Clearly α-synuclein plays a role (once dysfunction occurs), but answers as to how/when/where/why remain speculative. The first sentence on the subject on the MJFF site states, "Alpha-synuclein is a protein whose function in the healthy brain is currently unknown." If you have it figured out, however, the community anxiously awaits your brilliant revelations!
So having been called on your unjustified conclusions and lacking any effective reply you resort to an attempt at an ad-hom. And then you fail even at that! You are actually suggesting Glenn Beck as an authority on something? It figures.
Projection. You are the only one present who demonstrably and repeatedly jumps to unwarranted conclusions.
Your "contributions" to actually helping anyone else here with this condition are nonexistent. You use this forum merely as a place to stroke your own ego. Get a life.
PB... The original post floated the idea of setting up a "buy group" for PRX002/RG7935. My "contribution" was to spare the prospective buyers club some wasted time and energy by highlighting (with details from MBA's own link) that such efforts would be premature. The only fractured ego in the entire exchange was that so deftly displayed when you chimed in with ("contributed"?) your vague (and juvenile) "wrong" - void of any specifics of course.
So I want to understand this and here is how I interpret the info:
Alpha synuclein (ASN) is one of the most common proteins in your brain – it makes up about 1% of the protein in each neuron. It is very plentiful. What does alpha synuclein do? One thing we know is alpha synuclein is involved with normal synaptic functioning. More recently, we have learned that alpha synuclein is playing an important role in the handling of vesicles at the synapse. It acts as a protein buffer, helping to cluster vesicles at the synapse without affecting the release of the chemical messengers.
That is my basic understanding and I find it helpful to follow this blog:
And I reached out to Simon, the research scientist who runs the blog, and asked about the PASADENA study and expressed my concerns about indiscriminate removal of ASN. Here is what he shared:
"It is important to understand that the approach the researchers are using in the PASADENA study is not ‘indiscriminate’ in its removal of alpha synuclein. PRX002 (the drug being tested in the PASADENA study) is an antibody-based treatment that targets a specific aggregated (or clustered) form of the alpha synuclein protein which is believed to be toxic. It does not affect normal (un-aggregated) alpha synuclein. Exactly what PRX002 is targeting (the precise epitope) is a trade secret for company running the trial: Prothena.
As to the long term consequences of this approach, it all depends on where you stand in the great ‘alpha synuclein’ debate. If you think that aggregated alpha synuclein is the bad guy in PD, then removing it is probably a good idea. If, however, you think that aggregated alpha synuclein is simply an innocent man getting caught in the wrong place at the wrong time, then maybe it’s not such a great idea to remove it. There is some evidence to suggest that the aggregated form of alpha synuclein may be a defensive mechanism inside the cell – playing a role in protecting cells from viruses
(scienceofparkinsons.com/201.... Only time will tell if the PASADENA approach will work. One concern I do have with the study is that the clearance of alpha synuclein alone may not be enough. Perhaps they also need a anti-inflammatory or neuroprotective approach to real slow/stop PD. Follow up studies will be required to address this. Interesting times for Parkinson’s research."
bassofspades you hit on my primary question with the initial results from the phase I trials. The first PASADENA trials, for example, cite success in cleaning out ASN clumps but those being injected showed no improvement in symptoms whatsoever. I had to do a lot of digging to find that info because the first studies are really aimed at "safety" and making sure no one is going to have an adverse event - or worse - die as a result of taking the drug. So they talk a lot about the success of the safety trial because no significant adverse medical events occurred. However, we learn a lot about symptomatic impact in a safety or phase I trial, even though that's not the primary purpose in phase I. The argument is that it might slow or halt progression but then I think it would suggest improvement of symptoms. Yes? No?
We saw amazing improvements in the Phase I Nilotinib trial for example. I also think and agree with others that clearing ASN clumps may help us find a path to a cure but we need more info to understand exactly what is the best way to do it.
I am considering engaging in the PASADENA study and am considered a candidate but these are the things I am weighing personally.
P-oui, I am also considering engaging in the Phase 2 trial for PRX002 and considered a candidate. My MDS thinks the risk outweighs the benefit. Did you make a decision to participate or not?
I can't get into the study because I just passed my 2-year anniversary since diagnosis - I couldn't believe it. I think it is worth the risk, but I took too long to decide.
The trial is due to complete in 2020. Interested PWP should sign up for the trial. Inclusion and exclusion criteria here: clinicaltrials.gov/ct2/show...
They want early stage PD with bradykinesia which seems like an odd combination.
Thanks for this. If ever there is a breakthrough, I'd consider looking for a lab or compounding pharmacy to make some. Better than waiting 5 - 8 years.
This medication is an antibody - a large complex molecule that cannot be made by an ordinary drug manufacturer or compounding pharmacy. unlike, say, nilotinib. I am afraid we are going to be stuck with Roche/Prothena and that this will be pricey.
It helps me not to waste my time, because the lasts weeks my symptoms are increasing : mentally I'm a bit more aktiv , motivated (due to LDN at night ?) , but Motorik symptoms not better : rigidity the whole right side (some parts minimal, but still...)
And as I'm still working , cannot lose much time...
Does anybody of you have experience with the Coimbra-Protokoll ???
What are your benefits with B1, and after how much time ?? (or can I read it in another post ?)
ANYONE IN THIS TRIAL: Phase 2 trial, dubbed PASADENA. It will enroll 300 people who have been diagnosed with PD within the last two years but are not yet taking dopaminergic medication. They can be on a monoamine oxidase-B inhibitor such as rasagiline or selegiline.
Roche chose this population based on clinical data from the Parkinson’s Progression Markers Initiative and other studies that measured rates of change on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). “We think at this point in disease there is the highest dynamic change in PD symptoms measured by the MDS-UPDRS, so we have a high chance of detecting a reduction in disease progression,”.
For the first year, one-third of the cohort will receive placebo and one-third a low dose of antibody, 1,500 mg. The remainder will take a high dose, which will vary by body weight—3,500 mg for people under 65 kg; 4,500 for those 65 kg or heavier. The high dose is roughly equivalent to the highest dose tested in Phase 1, 60 mg/kg, but transformed into flat doses to simplify administration, Boess said.
The primary outcome measure will be change on the MDS-UPDRS after one year
You all have probably already seen yesterday's edition of the Science of Parkinson's which discusses the 1st trial of PRX002.
park_bear, about 8 months ago you said you thought this was a large complex molecule that cannot easily be made by a compounding pharmacy. You know anything more about this drug, i.e., what the name of it is, what the molecular structure is, how we can identify it?
Antibodies are biological entities, made in cells (B-cells). Mice make them, rats make them, YOU make them. You can culture cells to make them in a lab, but as far as I know no compounding pharmacy could ever "compound" one.
To create anti-ASN antibodies what is probably happening is something (VERY ROUGHLY) like this: they are injecting mice with ASN, the mice are seeing it as an invader (like a germ) and thus making antibodies against it. Then they take mouse's blood, isolate the specific antibody...
*many, many steps here*
...VOILA! Ready to inject in people!
But you see? This is not a pharmacy thing. And actually, I think these are MONOCLONAL antibodies, even fancier--very specific, very pure.
As far as I know the trial is ongoing. I think the problem with any trial (besides that fact that they won't report results 'til they're done) is that they won't SEE results for a while, either! Think about it--it took years to make PD damage. Doesn't it make sense that unmaking it might take as long? Sometimes I look at these 6-week trials and think: they saw "no change"? What did they expect?
PS--It bugs me that you have to be <2yrs post diagnosis. It's stupid, IMHO. We all get diagnosed at such different times in our course. They should have a more objective measure. ARE YOU LISTENING TO ME, RESEARCHERS??? :o)
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