Medicine 3.0
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I wrote a post this past December outlining why I thought Chloe may have experienced drug-induced lupus. It’s been eight months since we stopped the TPO receptor agonists (Nplate and Promacta), and I am happy to report the following labs have officially normalized:
dsDNA
C3
B2 Glycoprotein-1 antibody (IgG)
Cardiolipin antibody (IgM)
AH50
Microscopic hematuria
The anti-histone Ab (IgG) is still present but has declined from 2.7 units → 1.5 units (considered weakly positive). Normal is considered to be <.9 units, so we are well on our way.
There aren’t any cases of drug-induced lupus anywhere in the literature secondary to either medication, although I did find reports of drug-induced antiphospholipid syndrome. It’s hard to say definitively what happened as there are so many other variables:
Improved her nutrition
Added supplements
Prioritized exercise/physical activity
Started sirolimus
But, the timing of her clinical and laboratory improvement seems to support this theory. You can read about that in the post below.
Unfortunately, her platelets haven’t improved (currently at 4,000). But, her thrombocytopenia happened long before the TPO receptor agonists were introduced.
We started sirolimus (rapamycin) three months ago and have been titrating slowly (a bit too slow, in my opinion). Currently, she’s taking 1.2 mg per day (oral solution). However, the bioavailability of the oral solution is not the same as that of the tablet. Much less is absorbed, and it’s not until the dosage increases to 2 mg that they become bioequivalent. Her trough concentration has only increased from 4.9 ng/ml (at the .5 mg dose)→ 5.6 ng/mL (at the 1.2 mg dose). Although she’s technically in the therapeutic range (range taken from transplant patients), there’s still plenty of room to safely increase her dose.
This past January, I was introduced to the many (possible) benefits of rapamycin after listening to a podcast from Dr. Peter Attia. This medication has a fascinating history (you should look it up if you’re a geek like me).
It was originally FDA-approved as an immunosuppressant for transplant patients. However, this immunosuppressant effect seems to be dose-dependent. At lower doses, it’s believed to have an immunomodulatory effect and is thought to improve immune function. It also shows promise in various other diseases due to the downstream effects of mTOR (including longevity in healthy humans). A quick search on clinicaltrials.gov shows 2,446 clinical trials (462 are active or will be active shortly).
But not everyone has bought into the hype. All our doctors have cautioned against its immunosuppressive properties and possible adverse outcomes associated with prolonged use. But, whenever evaluating a clinical study, it’s important to keep in mind the patient population from which the data is extrapolated:
Organ transplant patients
Prescribed a cocktail of immunosuppressants
Higher doses of sirolimus
This is a very different type of patient. Nonetheless, it’s where the data originates, so it’s applied in broad strokes. I’ve experienced this lack of individualized medicine throughout our daughter’s care.
It’s impossible to predict how Chloe will respond. If she has a great response, she is still only a sample size of one. But, I will say that since starting sirolimus, she hasn’t had a single upper respiratory infection. For all you parents out there, you can appreciate how impressive that is for a toddler (she turns two next month), especially one who should have a suppressed immune system.
As an aside, Sirolimus could be beneficial in mitochondrial disease as it’s thought to help increase complex 1 activity in the respiratory chain and assist in autophagy/mitophagy.
As I said, I was introduced to Dr. Attia as I began researching sirolimus. However, I have continued to consume his work after realizing we share many of the same beliefs about the current state of our healthcare. If you’re looking for a good read, I recommend his book Outlive: The Science and Art of Longevity (I have no affiliation).
One concept I feel worth mentioning is that of medicine 3.0. I took the following excerpt directly from one of his podcast episodes:
“Medicine 1.0 is when we had no idea of science. Science is a way of thinking—not a person, not an answer—science is a process. It’s a way that we look at the natural world around us and formulate hypotheses about what explains them based on the physical principles of the universe.
We design experiments to test those hypotheses and measure the results against the predictions of the hypotheses. Then, we iterate and correct. However, evolutionarily, we’re not naturally wired to do that.
Before the invention of this idea, nothing that existed in medicine could be tethered to science. Any time something happened, you had to come up with an explanation. But none could be linked to scientific facts or verifiable or testable hypotheses.
This is where you had all sorts of crazy ideas.
Medicine started to change in the late 17th century with Francis Bacon. However, the full transition to medicine 2.0 didn’t take place until the advent of germ theory in the late 19th century.
This was the breakthrough of medicine 2.0, which comes from three things:
The advent and acceptance of germ theory
The process of scientific thinking
The statistical machinery to enable randomized control trials (the “crown jewel of medicine 2.0”)
But we’ve reached a plateau with Medicine 2.0. Although it has been an amazing development, I don’t want to minimize it; I want to acknowledge that it has really peaked.
It’s been very good at dealing with acute conditions, for example keeping patients alive as long as possible after a car accident, a life-threatening infection, or suffering an MI. You want to make sure someone doesn’t die and you want to keep them alive as long as possible in that acute phase.
We have reached the limits of medicine 2.0 capacity, and if longevity is something we are aspiring for, we need a new strategy. We need a fundamental shift just like 1.0 to 2.0. We need to go from 2.0 to 3.0.
Medicine 3.0 is basically predicated on evidence-informed as opposed to evidence-based guidelines. It is predicated on absurdly early preventative measures for chronic conditions (not acute conditions), which are now the dominant source of morbidity and mortality. Medicine 3.0 has to be highly personalized.
We’re not yet in medicine 3.0, but we’re in that transition phase, and I think we should be accelerating that.”
My biggest gripe with our daughter’s care was the lack of individualized medicine that took place. She was an outlier from the start but was put into the same box as every other patient. It very much felt like our doctors were taking a board exam, as we were forced down the same algorithm used for 100% of patients. To be clear, this is no longer the case, and every decision is now a thoughtful discussion.
A community member said my experience reminds her of the Institute of Medicine report To Err Is Human, which says, "…the problem is not bad people in health care--it is that good people are working in bad systems that need to be made safer."
Unfortunately, our education teaches us to diagnose and treat after a disease is already present. But we are never taught how to keep healthy people healthy. The best we have are screening and preventative tests. But even these tests look for early signs of disease (meaning the disease is already present).
Individualized and evidence-informed medicine is a lot more work and a lot more complicated. But I believe we are worth it.