Another bright SPARK

[WinnieThePoo]

As I write , I am newly brim full of BIIB054 after 2 months missed due to "le confinement" as the lockdown is called in France. Nice to be back with my team. And to get topped up. Mrs WTP is convinced things became worse when the perfusions stopped, although after a confusing few weeks dabbling with B1, and changing pramipexol dose, as well as having to tackle a corneal graft rejection episode, the last week has been my best for a long time - almost PD symptom free. It will be interesting to see how I am topped up with SPARK

[Fed1000]

Keep it up Winnie.

[redhawk1]

Stay the course!!! You are at the tip of the spear, Winnie!!!

[park_bear]

alzforum.org/therapeutics/b...

"BIIB054 binds to α-synuclein residues 1-10, with 800-fold higher affinity for aggregated over monomeric α-synuclein. The antibody inhibits α-synuclein spreading in cell-based assays, and slows pathology and motor symptoms in mice"

[WinnieThePoo in reply to park_bear]

Pass the cheese 🙂

Hoping for a bit of binding in me. Let's hope no more missed infusions. Sue was convinced things improved on the switch to year2 infusions and deteriorated when I missed sessions.

[sharoncrayn in reply to WinnieThePoo]

Interesting hypothetical connection between ALZ and PD.

The issue is: is this primarily for cognitive decline as seen in many PD patients? or does it include motor functions as well?

DaTscan comparisons should be interesting across the 3 dose arms.

Sharon

[WinnieThePoo in reply to sharoncrayn]

I confess I thought the big issue was is a-syn the assassin or the paramedic? And then of course all the BBB stuff .

What intrigues me is why the protocol was changed and why it's unreported and not updated on the trial website

[sharoncrayn in reply to WinnieThePoo]

"What intrigues me is why the protocol was changed and why it's unreported and not updated on the trial website"?

Answer: Because they weren't getting the outcomes they expected and wanted.

Frankly, this CT reminds of a human theoretical micro-cell biology trial. Look at the primary outcomes/end points. Note that the DaTscan is a secondary end point without a "baseline" scan required before inclusion that I can see. You really have to wonder why not. At least I do.

I hope it works for you....whatever dose arm you are in.

Sharon

[WinnieThePoo in reply to sharoncrayn]

There were baseline datscans and MRI scans.

The change is that low dose and placebo switch to medium or high dose for the 2nd year. So I can be sure I am now in medium high dose.

And we have been offered the opportunity to stay on the drug in what I think will be an open label extension

[sharoncrayn in reply to WinnieThePoo]

So your DaTscan confirmed your PD? Did you get a copy of your analysis (i.e. your loss of dopamine transporter activity)?

[WinnieThePoo in reply to sharoncrayn]

I have a report and a set of photos. But I'm pretty sure the main photo the report was based on is on this thread healthunlocked.com/parkinso...

[sharoncrayn in reply to WinnieThePoo]

If I can translate your comment: nothing changed from 2 years ago.

Note: nothing about whether or not the "depletion" has changed, which was my question.

So did the receptors show more depletion two years later, or did the neurologist for SPARK even discuss this issue in his/her notes?

"Scintigraphic examination confirms a net depletion of of the presynaptic dopamine receptors, in a bilateral manner but more noticeable on the right. This picture is characteristic of Parkinsons Disease"

[WinnieThePoo in reply to sharoncrayn]

Sorry. I hadn't properly understood your question. I am effectively only 15 months into the trial and have been asking without success to see and discuss my trial datscans.

I say without success but what I of course mean is without cracking the french paperwork defences. I think I have now cracked it and my trial physician is writing to my clinical physician to discuss with me all trial datscans at my next appointment in December (when I will have had the week 78 scan.)

The one in that thread is my diagnosis scan which qualified me for the trial.

I think mine are going to show a depletion with evidence of progression on the left side for the first 12 months. But i think that i was in placebo or 250 for the first year. Things are different year 2.

My interpretation of the change in protocol is there were no statistically significant changes at 250mg, so they are only interested in 1250 and 3500, where there were.

[sharoncrayn in reply to WinnieThePoo]

I would agree that they found nothing significant at 250 mg, i.e. the belief in the old adage "dose dependent" efficacy. We shall see.

[WinnieThePoo in reply to sharoncrayn]

Curiouser and curiouser! I'd been working from memory. I've just read the current trial site, and you are right. Just the primary and secondary you mentioned. If you look in the tabular view you can see the original outcomes.

It's not like Biogen don't know how to pull an expensive trial if it's not working. So given safety can pretty much be taken as read at this stage, why are they riding the datscan horse?

And given the data was updated feb 2020 and the protocol was changed in may 2019 why does it still say 250mg will stay on that dose in year 2 when the protocol says, with placebo, they change to 1250 or 3500?

And why the "opportunity to remain on the drug" at the end of the trial?

Baffled of Quillan

[sharoncrayn in reply to WinnieThePoo]

Biogen should have explained to the participants why they have changed the parameters of the CT and what those changes are and how they may or may not effect the participant's health and well being. Unfortunately, some CTs are run as if the humans are nothing more than stupid guinea pigs.

"why are they riding the datscan horse?" They aren't. It is a secondary.

"why the "opportunity to remain on the drug" at the end of the trial?" Because Biogen has no liability for extending it. Plus they believe in the likelihood they will obtain additional data on long term use from some participants without any additional costs.

Sharon

[WinnieThePoo in reply to sharoncrayn]

On verra 😉

[Hikoi]

Glad you made it through le confinement

[WinnieThePoo]

If nothing else, it sure fixes constipation! Although a 4-weekly intra-venous infusion, especially for someone with shy veins is probably a bit of a sledgehammer to crack a walnut just to fix constipation 😂

[WinnieThePoo]

And sense of smell?

[sharoncrayn]

What is your opinion after 3 months of "Sparky goes to Paris"? "Almost symptom free?" or "same old; same old"? or "why did I ever participate"?

Honesty is always the best policy.

Sharon

[WinnieThePoo]

Currently I have stopped pramipexol and whilst far from symptom free, am pretty comfortable. The drug is intended to slow or stop progress, not reverse the disease or have any symptomatic relief. It's really hard to say how my disease would have progressed without the drug, but for now it's ok, without medication.

I have been offered, and accepted, an 18 month trial extension