This is awesome work. But some obvious questions weren't asked or answered.: 1. Test retest reliability. People who come up positive, what percent of the time do they come up positive on repeating the test a week later? Are there time of day variations? Are there any indication that the level of AS in spinal fluid varies at all, or ever decreases? 2. Do people who aren't diagnosed yet and don't have symptoms ever show up positive? Does that correlate with later PD diagnosis, and how long after? 3. You mention detecting a-synuclein in the spinal fluid. But are you detecting the normal type, or the misfolded type? 4. Why do you have to add in normal tagged a-synuclein to make the test work? This wasn't explained clearly . 5. Upon autopsy, do AAS negative patients also not have misfolded a-synuclein in their brains? 6. What about false positives? What percent of healthy controls show up positive on AAS? 7. How much does it cost? Please mention this. 8. How much spinal fluid does it take? When you draw, do you draw enough to test multiple times, so that retesting can be done with improved verisons in the future? 9. You hinted you had preliminary data that AAS can also be used to measure progression. Why the secrecy? If you've been doing this for 5-10 years I'd expect you'd have hundreds of patients who have had repeated test separated by years. Very simple question: do people who had progression as measured by MDS-UPDRSIII also have progression in "how much" AS they have? And the converse: are there people who DO have symptom progression, but no AAS progression? You must have this data. Please mention it. Great work! This is going to be amazing in advancing the war against this disease.
I'd express the value of this for clinical trials more clearly this way: "All current and past trials have been done on a mix of people, 70% with "normal" A-Synuclein PD, 15% genetic, and 15% AAS-negative (with non-standard AS in spinal fluid). Since this latter group's disease is likely caused by different mechanism, this has polluted ALL past research, and potentially will have obscured any past treatments which WOULD have worked in any subset of the population, either AAS positive, or AAS negative. Furthermore, it is *completely* expected that we actually may have already tested treatments which fully arrest progression - but their viability wasn't provable on a mixed population and therefore they were likely abandoned. This leads to the obvious question: are past or ongoing major clinical trials going to re-evaluate their populations? Imagine a trial which worked amazingly - say, 50% better than placebo for AAS negative but no effect for AAS-positive. Naively, this would probably not count as statistically significant - but now, we know that if that 15% *just so happened* to be AAS negative, that treatment might have actually been amazingly effective on that population. Similar story for AAS positive. For recently complete & failed, or current trials, this could be a vital way to improve their interpretability. Have you talked to any large organizations to pitch this? Even if not definitive, it could be a relatively easy way to salvage very expensive past failed work.
@@olivierrousset6581 Yeah, reading the paper more closely though, the rate of Clinical PD + SAA-negative is pretty low actually. But among people with a normal sense of smell, apparently 40% or so have no a-synuclein. It will be absolutely amazing to see if those people really do have a different pathology, progression, etc. This could break down into two or more diseases, which may end up being easier to treat separately!
God bless Michael J Fox and his family.
Thank You
This is awesome work. But some obvious questions weren't asked or answered.:
1. Test retest reliability. People who come up positive, what percent of the time do they come up positive on repeating the test a week later? Are there time of day variations? Are there any indication that the level of AS in spinal fluid varies at all, or ever decreases?
2. Do people who aren't diagnosed yet and don't have symptoms ever show up positive? Does that correlate with later PD diagnosis, and how long after?
3. You mention detecting a-synuclein in the spinal fluid. But are you detecting the normal type, or the misfolded type?
4. Why do you have to add in normal tagged a-synuclein to make the test work? This wasn't explained clearly .
5. Upon autopsy, do AAS negative patients also not have misfolded a-synuclein in their brains?
6. What about false positives? What percent of healthy controls show up positive on AAS?
7. How much does it cost? Please mention this.
8. How much spinal fluid does it take? When you draw, do you draw enough to test multiple times, so that retesting can be done with improved verisons in the future?
9. You hinted you had preliminary data that AAS can also be used to measure progression. Why the secrecy? If you've been doing this for 5-10 years I'd expect you'd have hundreds of patients who have had repeated test separated by years. Very simple question: do people who had progression as measured by MDS-UPDRSIII also have progression in "how much" AS they have? And the converse: are there people who DO have symptom progression, but no AAS progression? You must have this data. Please mention it.
Great work! This is going to be amazing in advancing the war against this disease.
👏👏👏👏
I have suggestion, please mention the speakers in this webinar.
its good breakthrough how much accurate this markers for the detection of disease
I'd express the value of this for clinical trials more clearly this way: "All current and past trials have been done on a mix of people, 70% with "normal" A-Synuclein PD, 15% genetic, and 15% AAS-negative (with non-standard AS in spinal fluid). Since this latter group's disease is likely caused by different mechanism, this has polluted ALL past research, and potentially will have obscured any past treatments which WOULD have worked in any subset of the population, either AAS positive, or AAS negative. Furthermore, it is *completely* expected that we actually may have already tested treatments which fully arrest progression - but their viability wasn't provable on a mixed population and therefore they were likely abandoned.
This leads to the obvious question: are past or ongoing major clinical trials going to re-evaluate their populations? Imagine a trial which worked amazingly - say, 50% better than placebo for AAS negative but no effect for AAS-positive. Naively, this would probably not count as statistically significant - but now, we know that if that 15% *just so happened* to be AAS negative, that treatment might have actually been amazingly effective on that population. Similar story for AAS positive.
For recently complete & failed, or current trials, this could be a vital way to improve their interpretability. Have you talked to any large organizations to pitch this? Even if not definitive, it could be a relatively easy way to salvage very expensive past failed work.
Exactly my thoughts!
@@olivierrousset6581 Yeah, reading the paper more closely though, the rate of Clinical PD + SAA-negative is pretty low actually. But among people with a normal sense of smell, apparently 40% or so have no a-synuclein. It will be absolutely amazing to see if those people really do have a different pathology, progression, etc. This could break down into two or more diseases, which may end up being easier to treat separately!
Are essential tremors part of this study?
Can you use Ai to help figure out what's going on?
Who are the speakers name?
She mentioned the names at the beginning of the video
Could Neuralink help in fight for a cure?🤔🤔🤔🤔
This research is on some SHAKY grounds.
#Boring