The tree · Broken proteins and waste
A drug stops a misfolded protein piling up in the heart and extends life
Transthyretin is a blood protein that, in many people over seventy, starts to misfold and settle in the heart muscle as a stiff waste, until the heart fails. It is one of the clearest cases of ageing damage from a broken protein, and until 2019 nothing treated it. Tafamidis, a pill that holds the protein in its proper shape so it cannot settle, cut deaths by about a third over thirty months in a controlled trial of 441 people reported in 2018, and the United States regulator approved it on 3 May 2019. It does not remove what has already settled; drugs that do, by getting the immune system to clear the deposits, were in late-stage trials when this was written.
What would count
A controlled trial in people reports that a drug which stops a misfolded protein from piling up in the body, or clears what has piled up, lowers deaths or hospital admissions from the disease it causes, in a peer-reviewed report. For the clinic rung: a regulator approves such a drug for that disease. For wide use: available by prescription in several countries and taken by a substantial share of eligible patients.
Who settles it: The peer-reviewed trial report; the regulator's approval record; published uptake figures for the wide-use rung.
Where it stands
In clinical use. Reached 3 May 2019, on the record of accessdata.fda.gov. Next rung within 1 to 5 years. The year the model reads for it is 2019, the year it reached the clinic; what has happened is not drawn.
When it reaches the clinic: the project's estimate
This is the one thing on this page that is a judgment rather than a record. It is already in the clinic, so the model reads a known year; the estimate below is for the rungs still above it and feeds nothing. Set 16 October 2026, a first pass awaiting an outside review.
| Rung | No earlier than | Most likely | No later than | |
|---|---|---|---|---|
| In wide use | 2027 | 2030 | 2045 |
Why. The drug has been prescribed for seven years and competitors (a second stabiliser, gene silencers, and the deposit-clearing antibodies) were arriving when this was written, which brings prices down and widens use; the likely year for wide use is 2030, the earliest allows that it is already there by the test's standard once uptake is counted, and the latest allows for the price keeping it a specialist drug for another two decades.
Changes to this record
None since it was written on 16 October 2026. Every change to the stage or the estimate lands here with its date, the old value, the new one and the reason, and a change to the estimate never happens because a number looked wrong: it needs a dated reason and a source.
The last readings
- 17 October 2026 Quiet
Nothing in the window bears on the wide-use test: no uptake figure, no new approval and no new trial report dated 2026-10-10 to 2026-10-17 was found. The only patient-scale figure seen is Pfizer's 2019 estimate of about 100,000 people with the disease in the United States with one to two per cent diagnosed, which is too old to count. Two things older than the window are not in the leaf and do not change the rung: a gene silencer, eplontersen, missed its main measure of cardiovascular deaths and events against placebo in the CARDIO-TTRansform trial (reported at the European cardiology congress with a New England Journal of Medicine paper; the American College of Cardiology's summary is dated 2026-08-24), which bears on the estimate's expectation that silencers would widen use but leaves the approved silencer vutrisiran in place; and the deposit-clearing antibody ALXN2220's Phase 3 trial (ClinicalTrials.gov NCT06183931) lists an estimated primary completion of 2027-12-06, so the "late-stage trials" line in the description holds. Pfizer's plan to withdraw the low-dose tafamidis capsule in the United States was seen in trade coverage of uncertain date and is a product decision, not an uptake record.source 1, source 2, source 3
What the story so far says about it
No promise, self-experiment or logged paper names this one yet.
Notes
The branch's own line asks for waste cleared throughout the body; this drug stops one protein in one organ, and the branch's notes say so. It is here because it is the first approved drug against an age-related protein deposit, and because it treats a disease that is mostly a disease of old age even though the regulator's notice calls it rare. It is widely prescribed in rich countries at a very high price, which is why the record keeps it at clinical use and not wide use until uptake figures say otherwise.
Not yet verified
These facts in the record were written from memory or from a secondary source and have not yet been checked against the paper, the regulator's record or the registry. Nothing here is presented as settled until it is cleared, by checking it and either deleting the line or correcting the record.
- No animal rung is recorded: the discovery work (Kelly and colleagues at Scripps) was done largely in the test tube, and a search of the literature on 2026-10-17 found no clean, dated animal report to record.