News from our SFO Meet-up

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Julie G
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Re: News from our SFO Meet-up

Postby Julie G » Tue Jun 02, 2015 9:50 am

Interestingly, Teezer, Dr. Rao (from The Buck) has just written a paper outlining evidence that one of the strengths of the E4 allele was the excellent protection it provided from "rampant infectious disease." Great paper, Russ; evidence that a widely variable nutrient dense omnivorous diet with periods of fasting may be the best match for our ancestral allele?

Poor choice of words, ApropoE4 ;) I was trying to convey the idea that if Orbimed, the leading healthcare venture capital firm, believes this has the ability to work... I feel great confidence- as THEY clearly wouldn't make an unwise bet.
https://www.cbinsights.com/blog/healthc ... op-mosaic/

I just had a few more thoughts to share about our meet-up. I was thrilled to hear the depth of the science behind Dr. Bredesen's paper/MEND therapy which Stavia has briefly detailed here:
Basically the premise is that there is an interaction with apoe4 and pro inflammatory mediators such as RelA which tips the system towards a pro inflammatory state in which NFkB is dominant and SirT1 inadequate. This causes neurones to degenerate. Apoe4 does this by entering the nucleus and binding to 1800 gene promotors. They have grouped the effects into his programme's 36 "holes" which they are trying to plug thru their various modalities.

We will link that talk so that all will soon have the opportunity to see for themselves. Dr. Bredesen has now worked with 30+ patients some of which had either FDG-PET or amyloid scans indicative of AD- who've all shown reversal of cognitive decline. Many were previously high functioning physicians, lawyers, etc. who were able to return to work. I found it fascinating that symptoms returned when patients veered off of the protocol, but reversed upon resuming. This is not unlike what many report here. Dr. Bredesen is working to collect rigorous scientific evidence of the efficacy of the protocol; very difficult with a multifactorial, individualized approach. It will take time. John Walker, the CFO, of Muses Labs was also present to meet with us. They are working hard to make this more widely available. From everything I've learned, their approach is the best synthesis of strategies we've discussed here; providing a blueprint for our members until Pharma is ready.

The Buck truly rolled out the red carpet for us. Chef Rebecca Katz, author of "The Healthy Mind" cookbook provided a delicious lunch: greens, nuts, seeds, salmon, a variety of unsweetened teas and a yummy looking bite-sized dark chocolate dessert.

The entire experience was surreal. I wish you all could have been there; especially the old-timers. Our members were truly honored and celebrated. IMO, Dr. Bredesen is a great man because he was very comfortable shining a spotlight on our group's efforts. Many other scientists would have written us off as "crazies," instead he was fascinated by our journey and grandly acknowledged it. Dr. Bredesen deemed our assembly an historic moment. It felt like it.

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Re: News from our SFO Meet-up

Postby GenePoole0304 » Tue Jun 02, 2015 10:07 am

good to hear some are the inspired.

now the E4 causing Alz.. well there are theories and weird ones but wasn't the first case a E3?

Dr Google has a big story on longevity and it is not so bad at all

http://genomics.senescence.info/longevi ... hp?id=APOE

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Re: News from our SFO Meet-up

Postby bentkat » Tue Jun 02, 2015 10:34 am

I am enjoying all the posts on your Days in May. I have Rebecca Katz cookbook and all the recipes I have prepared have been winners. Nice to hear about the lunch she prepared for you. Being a foodie, I'd love to hear about your other meals. The Bay Area offers fantastic food.

I try to practice Dr. Bredesen's protocol & hope to hear from Muses Lab, sometime this year. It would be nice to hear comments from you chosen few that are in the Muses Lab program.

Kathryn, the bent-kat

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Re: News from our SFO Meet-up

Postby ApropoE4 » Tue Jun 02, 2015 11:22 am

Juliegee wrote:Poor choice of words, ApropoE4 ;) I was trying to convey the idea that if Orbimed, the leading healthcare venture capital firm, believes this has the ability to work... I feel great confidence- as THEY clearly wouldn't make an unwise bet.
https://www.cbinsights.com/blog/healthc ... op-mosaic/


In a way, I think Orbimed is in it because they believe the structure corrector alone isn't good enough and will require coupling with other forms of therapy that are more lucrative. The commercial issue with these small molecules is that there's a very low cap on their market prices because they're just very easy for labs to synthesize and therefore unlicensed versions will show up very quickly.

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Re: News from our SFO Meet-up

Postby aphorist » Tue Jun 02, 2015 11:56 am

In a way, I think Orbimed is in it because they believe the structure corrector alone isn't good enough and will require coupling with other forms of therapy that are more lucrative. The commercial issue with these small molecules is that there's a very low cap on their market prices because they're just very easy for labs to synthesize and therefore unlicensed versions will show up very quickly.


Is there a patent on the structure corrector and a molecular scheme available? Isn't the structure corrector based on an existing natural metabolite? If so, any idea what it is?

thx

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Julie G
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Re: News from our SFO Meet-up

Postby Julie G » Tue Jun 02, 2015 12:09 pm

Good question, aphorist. I don't know for certain, but I'd be shocked if this wasn't patent protected in some way.
In a way, I think Orbimed is in it because they believe the structure corrector alone isn't good enough and will require coupling with other forms of therapy that are more lucrative.

Interesting, that's sort of the idea of the protease inhibitor...but you may be thinking beyond that- to amyloid inhibitors, etc?

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Re: News from our SFO Meet-up

Postby Tincup » Tue Jun 02, 2015 5:12 pm

GenePoole0304 wrote:now the E4 causing Alz.. well there are theories and weird ones but wasn't the first case a E3?


I think the causal chain is like: E4 are more likely to fragment than E3's and E3's more likely than E2's. The fragmentation is the issue. They presented data with the fragmentation divided into bins - upper 50% and lower 50% by genotype. Even the least fragmented E4's would have been in the upper 50% category for the E3's. They then showed curves by genotype, of % with AD over time. The upper 50% got a lot more AD than the lower 50%. It is not deterministic, but certainly highly correlated...
Tincup
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Re: News from our SFO Meet-up

Postby circular » Wed Jun 03, 2015 12:07 am

"Dr. Bredesen has now worked with 30+ patients some of which had either FDG-PET or amyloid scans indicative of AD- who've all shown reversal of cognitive decline. Many were previously high functioning physicians, lawyers, etc. who were able to return to work."

This raises an interesting question. Will one's amount of cognitive reserve influence how successful the Bredesen protocol is for them? I'm not saying it should, but I wonder if there will be any sort of interplay there. I haven't seen reserve mentioned for a long time here, although I may have missed it. I think it should stay front and center with the other themes (stress, trauma ...). I once read that those with high cognitive reserve, once they get AD, progress through it quickly. Perhaps having higher reserve also allows for a quicker and better response to prevention and treatment interventions. Somehow it makes sense to me, but I couldn't begin to suggest the possible mechanisms if the symptoms are the same between two people, one with more reserve and the other less.

Definitely need to print all this out and attack it with my highlighter.

The video JulieAnnie posted recently mentions a little bit of some of this newer terminology and concepts, but of course not in the detail we're seeing it here.

Thanks All!
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: News from our SFO Meet-up

Postby karelena » Wed Jun 03, 2015 1:20 am

Unfortunately i missed Dr. Huang's lecture at the Gladstone because I had to get to the airport. Did he show data from the mice about their fragmentation and did the amount of fragmentation correlate with E4 vs. E3 and their performance on the maze tests?

On another note I just learned that a nurse practitioner that I know is a big proponent of functional medicine. I briefly looked at 2 books she had from the institute of functional medicine and to me it looks like members of this group could have written those books! It is all about genetics and inflammation and IR and basically everything we discuss on these forums. They have conferences that this nurse practitioner attends. I am going to learn more about it.

K

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Julie G
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Re: News from our SFO Meet-up

Postby Julie G » Wed Jun 03, 2015 8:35 am

Hi karelena! I love your take on Functional Medicine. Perhaps you'd consider a change in specialties? :D

Unfortunately i missed Dr. Huang's lecture at the Gladstone because I had to get to the airport. Did he show data from the mice about their fragmentation and did the amount of fragmentation correlate with E4 vs. E3 and their performance on the maze tests?

From what I recall, YES. Anyone who remembers more specifics, please chime in. Actually seeing the Morris Water Maze test was quite disturbing. The Gladstone team only uses female mice; as females are statistically more prone to develop AD. Observing the little 4/4 mice, working so hard, and not being able to find the hidden platform felt like an analogy for my life :roll: It was tough to see.

Even my husband was profoundly changed by seeing that and learning the science behind the E4 allele. He now feels a greater urgency to "fix" things. BTW, he was deeply impressed by you all: your obvious intelligence and commitment to working on our dilemma. Living in a house filled with equal parts physicians and engineers, with various other brilliant minds thrown in for variety; the conversations were educationally priceless- very different than bantering with pilots.

Friends, we met several amazing researchers from all over the world during our meet-up who would like the opportunity to take part in our community. I'm going to introduce them today. Please feel free to ask questions and use them as resources.


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