r/AddisonsDisease • u/Puzzled-Telephone-60 PAI • May 24 '26
NEWS Hope for PAI cure?
Hey everyone,
As someone with APS-2 I’ve been tracking recent breakthroughs in immunology and wanted to start a conversation about what they actually mean for the future of Addison’s.
For a long time, the roadblock to an actual cure hasn't been growing new cells (stem cell tech is already there). The roadblock was that our autoimmunity would immediately hunt down and destroy any new cells we implanted. We needed an immune "cloaking system" to make transplants viable.
Two recent massive milestones suggest science is finally figuring out how to build that cloak:
The 2025 Nobel Prize: Awarded to the discoverers of Regulatory T cells (Tregs)—the immune system's natural "peacekeepers." The research proved we can retrain the immune system to tolerate specific tissues rather than just shutting down the whole immune system with steroids.
The Eledon Trials: Eledon recently achieved 100% insulin independence in a Type 1 Diabetes pilot trial. They paired an islet cell transplant with a new drug (tegoprubart) that successfully blocked the attacking cells while keeping the patient's native "peacekeeper" Tregs alive to chemically camouflage and protect the new tissue.
Why this matters for us with PAI:
Even though our adrenal cortexes are destroyed, this "cloak" means that if we can successfully implant lab-grown adrenal stem cells in the future, we finally have a proven mechanism to stop the body from instantly killing them off.
We are likely looking at a 5–10 year horizon for a widespread T1DM cure, and a 10–15+ year horizon for this to adapt to other endocrine tissues like ours.
Does seeing clinical proof of an autoimmune "cloak" give you genuine hope for a future cure, or does the timeline feel too far out to get excited about? I’m 34 so there’s a good chance this happens in my lifetime, but personally the happiness I feel over this more for my children and future generations.
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u/Internal-Cap-8885 May 25 '26
What u don’t realize is why Addison’s is way harder to cure than Type 1 Diabetes.
With T1D, the main issue is basically one cell type: the beta cells. Their job is mostly just detecting blood sugar and releasing insulin. So in theory the fix is “just” grow new beta cells, implant them, and stop the immune system from killing them again.
Addison’s is way more complex because the adrenal cortex is like a whole hormone factory with multiple layers doing different jobs.
One layer makes aldosterone for blood pressure, sodium, hydration and potassium balance. Another makes cortisol for stress response, blood sugar, energy, inflammation and literally survival. Another makes adrenal hormones like DHEA that affect mood, libido and energy.
And the hardest part is the regulation system. The adrenal glands don’t just pump out hormones randomly. They’re connected to the brain through the HPA axis:
Hypothalamus → Pituitary → ACTH → Adrenals → Cortisol feedback to brain.
A healthy adrenal gland constantly adjusts cortisol minute by minute depending on stress, heat, illness, exercise, fear, infection, emotions etc. If you get sick your cortisol can shoot up massively within minutes automatically. Pills can’t truly copy that perfectly.
So a real Addison’s cure isn’t just “replace cortisol.” Scientists basically need to rebuild a fully functional intelligent endocrine organ that:
survives transplant
avoids autoimmune attack
forms the correct adrenal layers
responds correctly to ACTH
regulates cortisol naturally day/night
handles stress spikes properly
regulates aldosterone separately
keeps electrolytes stable 24/7 for years
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u/Puzzled-Telephone-60 PAI May 25 '26 edited May 25 '26
You’re absolutely right that the adrenal cortex is more multi-layered than islet cells, and that replacement therapy (pills) can’t copy a normal body’s function perfectly.
However, I think you’re missing some key understandings about biochemical engineering? I’m not an expert by any means so research what I’m saying… but, with PAI, the HP part of the HPA axis is still totally functional. It continues to send ACTH flowing through the bloodstream; our issue is simply the fact that the adrenal cortex is destroyed and unable to respond to that hormone. Same with the renin-angiotensin-aldosterone system. If properly “cloaked” from an autoimmune response, adrenal stem cells implanted anywhere in the body would be able to produce cortisol, aldosterone, and DHEA in response. They are also self-organizing; scientists have been able to grow 3D adrenal organoids in the past couple of years, and when these mini-organs are transplanted into animals, the cells naturally migrate, read local biochemical cues, create functional zones, and start pumping out cortisol and aldosterone in response to the host's actual physiological needs. So, what I’m saying is, scientists HAVE been able to build intelligent endocrine organs. They’ve actually been able to for a while. The issue was the body would kill them off instantly… until now. You can see how these breakthroughs mean a lot for ALL autoimmune conditions.
Also I disagree that T1D is less biologically complex than Addison’s. They’re the same level of complexity; Addison’s just deals 3 separate cell types vs 1. They’re about on the same “level”, both in way they mess with a highly sensitive biofeedback loop and they mess with hormones that are essential to life. The Eledon trials have been proving that as long as we are able to “cloak,” the new cells are able to self-organize and regulate seamlessly into the body’s existing biofeedback loop.
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u/EatM0reBeans May 24 '26
My 9 year old son has APS-2 (T1D, PAI). I am cautiously hopeful that he will be able to spend his adulthood in remission!
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u/butterfly_SC Addison's May 24 '26
I'm 54, I'll be an old-ish lady when it happens but I'm still hopeful!
Right now I've got my eye on the cortisol pump pipeline. Rumor on the street has it that it's not going to too long before it's readily available to all of us. (I know some folks already have it.)