#29

If you are going to require access that much, you use a PIC/PICC line.

Access with a regular cather is fine.

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#30

I’m just hunting around and learning more about the plasmapheresis market and technlogies and applications.

This submission to the FDA on the plasmapheresis clinical trial for alzheimers is really interesting and indepth… perhaps others here may be interested:

A MULTICENTER, RANDOMIZED, CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SHORTTERM PLASMA EXCHANGE FOLLOWED BY LONG-TERM PLASMAPHERESIS WITH INFUSION OF HUMAN ALBUMIN COMBINED WITH INTRAVENOUS IMMUNOGLOBULIN IN PATIENTS WITH MILD-MODERATE ALZHEIMER’S DISEASE

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#31

And I found this Takeda presentation helpful to understand the market better:

TakedaPlasma20190712-ir-presentation-on-pdt_final_e.pdf (915.3 KB)

#32

FWIW

Generic

2 viles, 500ml of 5% Albumin Human

$286.09 self pay

Screenshot_2023-05-26-19-05-04-130
Screenshot_2023-05-26-19-05-04-130720×1440 128 KB

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#33

Love this overall thread.

Capturing the health benefit of donating blood might be a good way to get health conscious young people to want to do it. (Perhaps a simple clinical trial on that could provide great data).

Does anyone know:

  1. what is the impact on ones blood stem cells/bone marrow if they are asked to keep generating new cells after each round of plasmapheresis, could they get depleted at an earlier age (reach exhaustion and even the Hayflick limit earlier)?

  2. what is the impact on one’s immunity? eg say one has good protection again Covid (either by recent vaccine or recent infection of both) and one then does a ton of plasmapheresis, will one lose a lot of those valuable antibodies? What about valuable t-cells and b-cells?

  3. what are the risks of communicable disease or cancer spreading via (young) plasma? via donor albumin?

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#34

Btw if one were to do this as chain of centers (perhaps franchised to speed growth) vs the at home route the centers could offer a lot of alternative configurations.

For instance, those wanting to optimize Apo B without or with less pharmacological intervention or just wanted to drive Apo B to child like levels could add on Lipoprotein Apheresis.

Same for those wanting to optimize their Lp(a).

I both cases the procedure involves the physical removal of lipoproteins from the blood:

And for Lp(a)

https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.116.307983

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Rapamycin and risk of cardiovascular disease
#35

There are facilities that offer “Lipoprotein apheresis”

The cost is why many do not hear/know of this procedure.

Difficult to get insurance to pay.

Self Pay is expensive, $2,500.00 average per treatment.

Review

Also Review;

https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.116.307983

And

Published: 17 February 2021

“LDL Apheresis and Lp (a) Apheresis: A Clinician’s Perspective”

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#36

It’s wonderful that you had the courage to go through this process, I actually chickened out! It isn’t risk free but Dr Kiprov is an expert in this process so probably as safe as currently possible.

My thoughts on your experience is that, with you not knowing which group you were in, you are probably not experiencing a placebo effect. Given that, and the fact that this is a pretty dramatic intervention, I would expect that you would actually notice some effect if you were in the actual exchange group.

I believe you wrote earlier that you didn’t notice any difference in how you felt. It will be very interesting to learn which group you were in.

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#37

FWIW

My biggest issue with any blood product is foreign particulate material{not just virus], material that are known {known to science] and unknown.

Example viruses can not be “filtered” out.

Even with testing, particles are there, just not detectable.

The risk potential{unknown] reward is more risk than potential reward.

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#38

Thanks for those links @Joseph

Exactly. That is the whole point of this thread - what models, logistics efforts could provide scale and lower cost.

The nice thing is that no new fda approvals are needed, etc.

Just adding that similar to all the longevity benefits @RapAdmin laid our in the first post and the other threads earlier in the week, the same model could also help within the number one killer (cardiovascular disease)

…,and that the ideas of how to scale and lower costs could be applied to both and if the centers/locations offered both they could provide and capture more value - hence making the logistic/business model stronger

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#39

All the evidence on this points to something in older blood being the issue (I think it is IL-10). On that basis it should be possible to create a replacement plasma without the bad things and with what is needed (albumin etc) and the work on doing this should not be that difficult.

People could then wash away the IL-10 (or whatever it is) from time to time.

Personally, however, I think the solution is to reduce the quantity of senescent cells.

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#40

Perhaps the model is plasmapheresis to take out the bad/old and the we need manufactured albumin and other potential young blood proteins, so not from a donors blood, but in a similar way to how one can make insulin in pharma factories.

That way there is no risk of being contaminated via donor material.

And the things that are added could be improved upon over time as we learn more and more. Eg in the beginning just albumin. Then GDF11, etc,

Below is a recent review of some of the young blood factors that have been identified and should be able to be manufactured in standard pharma biological manufacturing ways:

  • One of the first reported rejuvenating factors in young blood was growth differentiation factor 11 (GDF11)

  • A second young blood-derived rejuvenating factor, the bone-derived hormone osteocalcin

  • Within human umbilical cord plasma, tissue inhibitor of metalloproteinases 2 (TIMP2) and colony-stimulating factor 2 (CSF2 or granulocyte–macrophage colony-stimulating factor (GM-CSF)) were identified as two factors that decrease by early adulthood

  • This work revealed two factors capable of promoting synaptogenesis and dendrite arborization: the secreted matricellular proteins thrombospondin 4 (THBS4) and SPARC-like protein 1 (SPARCL1)

  • Glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1)

https://www.nature.com/articles/s41593-022-01238-8

#41

Although I think this is a good starter I think we need to work out why older people’s blood has things in it which cause problems. (I think it is IL-10).

My view (and apologies to anyone bored by this) is that almost all aging problems are caused by problems with gene expression. The problems are caused by a mixture of senescence burden (causing a reduction of Acetyl-CoA in the nucleus) and mitochondrial inefficiency (causing a reduction of ATP and Acetyl-CoA in the cytosol).

Hence creating new plasma is useful to reduce the effect of SASP, but won’t fix the mitochondria.

DNA damage is another issue which is less of an issue, but harder to fix.

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#42

I thought this was quite an interesting talk from Irina Conboy. She mentions that TPE removed senescent load in aged tissue

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#43

Joseph,

You bring up some good points, and I’m wondering if we can discuss this a bit and broaden this point and clearly identify the (potential) issues around the blood / albumin supply as its currently defined.

Problems with Existing Young Blood Plasma (Fresh/frozen) and Albumin Supplies:

1. Potential foreign particulate material { not just virus], material that are known {known to science] and unknown. (Joseph, do you see this as an issue both in albumin and young blood plasma (fresh/frozen)?

2. Poor availability and Suboptimized Young Blood Plasma: Other than a few groups that have hit the press (e.g. Jesse Karmazin and Ambrosia, etc., and now https://resurgencewellness.com/ that Bryan Johnson used in Dallas for his experiment) its hard to know if what groups are actually providing young blood plasma for sale or as a service. So - availability of any young blood plasma (fresh/frozen) is extremely low right now. But even then, when Ambrosia was offering its services it seems the key requirement was simply age. Now there is new research that shows that ideally you would want blood that is both young and healthy, but coming from an athletic person. Currently, as far as I can tell, nobody is providing this yet. See this research and news coverage:

History of Failure, Moral and “Optics” issues:

Another issue is that from a business standpoint, this may not be a fundable opportunity (the young blood business) because of its past failures, and morally questionable fundamentals, as was mentioned in the recent Bloomberg article on Bryan Johnson:

The so-called blood boy stigma around longevity-focused plasma transfusions has meant that few people who pursue the treatment discuss it openly. Besides the obvious vampiric quality to the process, the mechanics can seem elitist and unsavory. In most cases, a wealthier person is receiving the plasma of a much younger, less well-off person. The plasma donors typically receive about $100 in gift cards for a procedure that costs roughly $5,500.

and, as the founder of Ambrosia mentioned after the FDA clamped down on him (He then started Ivy Plasma, which also was closed a year or two later (not sure exactly why):

Jesse Karmazin, CEO of Ambrosia, recently opened a new venture and is continuing to sell 1 liter of blood plasma for $8,000 and 2 liters for $12,000.

“Ambrosia was dissolved, but Ivy Plasma is open for business. Ivy Plasma provides off-label plasma treatments, which is legal,” Karmazin wrote in an email to TMC Pulse. “I can’t comment on the potential risks or benefits of this treatment due to restrictions on off-label marketing of medications by the FDA.”

Literally sucking the blood out of poor people so old wealthy people can live longer is a tough business model to market and destined to poor press coverage. But - younger, healthier people (family and friends) donating young blood to help their older relatives live longer seems like a much easier sell… with none of the “yuck” factor.

So - perhaps this is an activity better provided by some sort of non-profit organization.

What Can We Learn from the Failures?

It seems that it would be very valuable to get some input from Jesse Karmazin… given he’s started and closed two of these related businesses. I check on Linkedin and he doesn’t seem to be updating his profile, and I’m only connected at the “3rd” level - so perhaps someone here who is more directly connected to him can contact him, find out what he’s up to, and see if he’s willing to share some information. Here is his profile: https://www.linkedin.com/in/jesse-karmazin-md/

Additionally, it would be valuable more generally to learn from what people have been doing in the young blood plasma and parabiosis trials done so far.

I noted this comment from one specialist, in this article: High risks and high costs for young blood donations to older people - TMC News

clinics selling plasma from young donors are not replicating the same experimental conditions, said Vivien Sheehan, M.D., Ph.D., assistant professor of hematology-oncology at Baylor College of Medicine.

One California-based company, Ambrosia, sold participation in a clinical trial that offered each client one liter of human plasma harvested from young adults. Ambrosia charged $8,000 for that one liter, but since the FDA warning, the company has shut down. The Ambrosia trial raised major safety concerns.

“I’ve never seen an alleged trial that only had one inclusion criteria: that you be over 35,” Sheehan said. “There were no other safety measures taken to make sure you’ve never had a transfusion reaction, to make sure you can handle the volume, to make sure you’re not hypercoagulable. There was nothing in there to protect the individual and screen out people for whom this would be more dangerous. … This was clearly just an advertisement masquerading as a clinical trial. I can’t emphasize enough how disturbing it is that patients are being put at risk for something that is so unproven. The thing that is proven is that plasma can kill you. The thing that is unproven is that it would have any benefit whatsoever, so the risk-benefit ratio is completely off.”

Creative Solutions to these Problems:

  1. Albumin to start with: It seems like albumin is relatively easily available and commercially sold (with a prescription) today for around $280/liter. This seems like it would be a good place to start, and could be used immediately.

  2. Longer term solutions with Young, Athletic Blood:

Umbilical Cord Blood: I’m wondering if Umbilical Cord Blood / Stem Cells might be something that could be used for this application? This is mostly tossed out today - perhaps it could be used as the ultimate in “young blood”? Umbilical cord blood | March of Dimes

Family Donations: Perhaps there is a model by which the elderly could encourage family members (Children, Grand Children, younger relatives) to participate in a young blood donation project?

Other ideas???

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#44

Big one, that truly would be scaled without constraints:

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#45

Does anyone have a sense of whether this is real or does not matter:

  1. what is the impact on one’s immunity? eg say one has good protection again Covid (either by recent vaccine or recent infection of both) and one then does a ton of plasmapheresis, will one lose a lot of those valuable antibodies? What about valuable t-cells and b-cells?
#46

Sure - synthetic biology for albumin is great, but such a product doesn’t seem likely to be available any time soon, and would require a major biotech effort. So - not really the purvue of biohackers.

And - Albumin at $280/liter seems pretty cheap and available, and perhaps the least of our concerns. I think most people here would be happy to pay $500/month for a 2 liter / monthly plasmapheresis treatment program with the currently available albumin 5%, so thats not the critical path item for our use of this technology.

#47

I think it is an issue in the immediate period after the TPE session. When I went into Dobrik Kiprov’s clinic they asked me when I had my last vaccine shot. I mentioned I had recently gotten a shingles vaccine (a day or two earlier), and they said there was a risk that the TPE would eliminate any benefits of the vaccine I had just taken.

So - yes - issues that need to be outlined clearly, researched and considered.

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#48

Was less thinking about cost, but rather taking out any risks of transmission of known and unknown types of communicable disease (as perhaps even other remnants, seeds of cancer?, etc) from the donor.

Especially if this is a repeat thing where one for longevity purposes will be getting exposure to many, many donors’ histories.

Personally, would be fine with doing blood “dialysis”, but would not want to keep exposing my blood system and body to things from so many other donors health pasts.

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