News from PrecisionLife Ltd.

This is a long (over 1h) interview and I was a bit put off by Cort’s style to start but it’s actually one of the more interesting interviews I’ve heard from PrecisionLife. Which makes me hopeful for how they present and communicate any findings in their upcoming paper

Points that stood out to me
  • why did PrecisionLife get involved with ME/CFS? Partly because nobody else was, so unlike their partnerships with other companies which remain more secretive, they could use us to show off their platform by publishing results and papers
  • why combinatorial genetics? Biology is complex, many diseases are complex and involve multiple factors, multiple genes, pathways and feedback loops which interact. Broadly speaking looking at combinations helps increase any biological signal in the data
  • they’re targeting small molecule generics, because they’re well known, well tolerated, easily obtainable, cheap and dosing is understood. So this helps fast track things compared to looking for new/novel
  • TLR4 and LDN, even if it only works on some patients, on a subset, if you can demonstrate to drug companies that you have a target (a gene) which is disease modifying and you have clinical validation that modulating this target in a certain has a clinical benefit and you’re demonstrating you can pick the patients it works on… that will get the industry interested in the market and the disease
  • positive words about the community of patients and researchers but also raises the need for scale, not just one or two people trying things
  • trials for 9 generics are designed, challenge is running them, they need partners as they are a small company and are looking at about 60 different diseases (across women’s health, obesity, neuroscience)
I’ll update with the second half later
 
I’ve skipped some of the discussion to focus on the bit people probably care about most, DecodeME data.
  • they have the data from 11,500 patients (smaller than full set as not everyone consented and there were some data QC issues)
  • They have 4 main datasets, UKB, UK Sano Gold LC, NIH All Of Us and now DecodeME
  • have previously replicated Sano Gold LC findings in All of Us, despite ancestry differences
  • now replicated their previous UKB findings in DecodeME data so confident in their methods and results
  • new preprint with results of their analysis of DecodeME data is coming in about 3 weeks (unsure when the interview was conducted)
  • PrecisionLife are seeing the same as DecodeME saw and more
  • 3 figure number of genes (so over 100) identified in DecodeME data
 
hotblack said:
I’ve skipped some of the discussion to focus on the bit people probably care about most, DecodeME data.
  • they have the data from 11,500 patients (smaller than full set as not everyone consented and there were some data QC issues)
  • They have 4 main datasets, UKB, UK Sano Gold LC, NIH All Of Us and now DecodeME
  • have previously replicated Sano Gold LC findings in All of Us, despite ancestry differences
  • now replicated their previous UKB findings in DecodeME data so confident in their methods and results
  • new preprint with results of their analysis of DecodeME data is coming in about 3 weeks (unsure when the interview was conducted)
  • PrecisionLife are seeing the same as DecodeME saw and more
  • 3 figure number of genes (so over 100) identified in DecodeME data
Click to expand...
See I'm more excited about what other people can do with this new paper than what precisionlife themselves are planning. Although that could pay off big time if thats how pharma get interested.

But really I want to see how these data complement DecodeME and Zhang and what the smart people here and in the research community make of it.
 
I'm also a bit skeptical about the claims of hetrogeniaty - I'm not saying there is only one illness under ME/CFS, there may well be more, but the whole 'there's 15 different subsets and all the treatments the community use actually work but only in subsets' thing always makes me a bit iffy.
 
In some ways I’m similar and I think we’d all like to find a single root cause and something which can just fix us all. Maybe we will, maybe it will be quick and something off the shelf works. But maybe it will be a new target requiring new treatments to be developed. So if we can find things which can help people until we get that, or it helps us understand more, it seems worthwhile.

To expand on this (or repeat myself) a bit, I’m looking at this more as a parallel effort than an alternative. Less about the arguments between there being multiple different diseases or one and more about different downstream variations of an underlying cause. We talk about these variations in biology and about the interactions of different systems all the time here. Even with daratumumab there’s the ‘oh well it works with people with certain NK cell populations’ argument.

So for me the idea that people’s variation in symptoms can be because some of the many different spinning cogs in the complex biological clockwork could be moving faster or slower than others seems logical. If we find one trigger that allows everything else to fall in to place, fantastic. But I’m not against looking at some of those individual cogs to help people feel better or to help us work back from there to understand mechanisms better either.

And yes the possibilities for getting drug companies and bringing funding and interest in to our condition seems interesting too.

My problem has always been I don’t understand what PrecisionLife are doing, they can’t explain it adequately to us. It’s a bit of a black box. Maybe that won’t change but they seem to have some decent relationships with people I do trust so we will see.
 
hotblack said:
To expand on this (or repeat myself) a bit, I’m looking at this more as a parallel effort than an alternative. Less about the arguments between there being multiple different diseases or one and more about different downstream variations of an underlying cause. We talk about these variations in biology and about the interactions of different systems all the time here. Even with daratumumab there’s the ‘oh well it works with people with certain NK cell populations’ argument.

So for me the idea that people’s variation in symptoms can be because some of the many different spinning cogs in the complex biological clockwork could be moving faster or slower than others seems logical
Click to expand...
I was thinking along these lines earlier before you posted this! Great minds!

The daratumumab example is good because it could be many different things - 2 different diseases, sub optimal drug effectiveness linked to NK cell levels, nk cell levels as a marker for something else etc.

My main beef with LDN is it often isn't clear how much its helping at all. My partner just went off it for five days due to prescription issues and felt worse. Is it because the drug was helping or because of withdrawals? Who knows. She has seemed a bit better on it generally. But identifying who will benefit (if anyone) could be really helpful. Id be much more inclined to try it, or mestinon or whatever if i had confidence i was likely to respond well.




hotblack said:
My problem has always been I don’t understand what PrecisionLife are doing, they can’t explain it adequately to us. It’s a bit of a black box. Maybe that won’t change but they seem to have some decent relationships with people I do trust so we will see.
Click to expand...
This is true. I wonder if, for example, Chris Ponting has been given a peek under the hood of their eldrich AI apparatus? Or whether it's a strict company secret like whats in coca cola (I don't think I want to know that one!)

If Chris or someone equally smart knows what they're up to and thinks the methodology is sound thats all I would need to know to feel confident. But industry secrets being what they are maybe their research partners don't even know under NDA or whatever.
 
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