Form a company around the outcome
Alzh.ai is a company in formation, founded on the ambition of a durable cure for Alzheimer’s disease. We are at the founder-and-mission stage. The immediate task is to assemble scientific leadership, select a first testable research question and define the evidence that would support or reject it. This founding case sets out the outcome we want to pursue and the questions that should shape those first decisions.
Respect what progress has taught us
Current treatments have advanced what is possible, but no known intervention cures Alzheimer’s. In a large randomised trial, donanemab slowed clinical decline in people with early symptomatic disease. That is an important distinction: a treatment can help while the disease continues to progress. For us, the unanswered question is what would be required to move from slowing decline to a durable change in its course, and ultimately to a cure. The answer cannot be assumed from a single promising mechanism.
Make the outcome concrete
The word cure needs a precise meaning. It must describe who benefits, at what stage of disease, by how much and for how long. Our starting standard would require lasting cessation of disease-driven decline, meaningful preservation or recovery of function, and evidence in people that benefit persists after treatment ends. The exact standard remains to be developed with scientific and clinical expertise. A useful standard must also account for safety, daily life and what happens when treatment ends. These are questions to resolve before making claims.
Follow the biology, without skipping the person
Alzheimer’s affects the communication and survival of nerve cells. Understanding the biological changes matters because it helps us choose what to test. But a molecular measurement and a person’s ability to think, remember or live independently are different kinds of evidence. Each proposed intervention needs a credible connection between the biological change it seeks and the human benefit it intends to deliver. Where that connection is uncertain, the uncertainty belongs in the research question.
Treat timing and recovery as central questions
The same intervention may face very different problems before symptoms appear and after substantial damage has occurred. Preventing loss, stopping further loss and restoring an ability should each be examined explicitly. We do not yet know which approach, or combination of approaches, could meet a curative standard. Being ambitious means remaining open to that complexity while staying disciplined about what any individual experiment can actually establish.
Start with the people and the question
The next step is to bring together scientific leadership with the expertise to challenge this case. Together, we intend to select the first testable research question and define what evidence would change our minds. Those decisions are still ahead of us. We want the purpose of the company to remain clear as the science develops, and every eventual claim to be earned through the work.
Four open research questions
Questions informing the founding case, with the public evidence behind them. They are a starting point for discussion with scientific leadership.
MechanismWhat must change to stop the disease?
Which biological processes would a curative intervention need to address?
What the evidence says
A phase 3 donanemab trial found slower clinical decline in people with early symptomatic Alzheimer’s. Both treatment and placebo groups still declined on average.
The open question
Which additional changes, if any, could produce durable disease arrest and meaningful recovery?
TimingHow early is early enough?
A cure must have a defined starting point: who it helps, and when.
What the evidence says
Alzheimer’s-related brain changes can begin years before noticeable symptoms. Early and advanced disease present different challenges.
The open question
When could intervention prevent further damage, and how much function could be recovered after symptoms appear?
FunctionWhat would it take to restore function?
Stopping damage and recovering an ability are separate scientific problems.
What the evidence says
Alzheimer’s disrupts communication between nerve cells and can lead to the loss of cells and their connections.
The open question
Which impairments remain reversible, and what would rebuilding useful brain function require?
EvidenceHow would we know it is a cure?
The standard must be clear before the result arrives.
What the evidence says
A biological measurement can help assess disease, but it is not automatically a direct measure of clinical benefit.
The open question
What combination of sustained benefit, safety and follow-up would justify a curative claim for a defined group of people?
Sources & further reading
Public evidence informing this case. The proposed direction and definition of success are our starting position.
- How Is Alzheimer’s Disease Treated?National Institute on Aging
- What Happens to the Brain in Alzheimer’s Disease?National Institute on Aging
- Alzheimer’s DiseaseNational Institutes of Health
- Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical TrialJAMA · Sims and colleagues · 2023
- FDA issues guidance regarding drug development for early Alzheimer’s diseaseUS Food and Drug Administration · 2024
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