A US government health research agency will pay up to $41 million over four years for a national study that aims to find ways to prevent or slow Alzheimer’s disease faster than usual, Mass General Brigham announced1. The money comes from the Advanced Research Projects Agency for Health (ARPA-H), part of the US Department of Health and Human Services1. The study will test drugs already approved for other illnesses, along with natural products, in people whose blood shows early signs of Alzheimer’s1.
No treatment has been tested in this program yet. What is new is the funding and the plan.
What happened
The project is called “Platform Trial for Biomarker-Guided Alzheimer’s Disease Prevention”1. It will be led by neuroscientist Rudolph Tanzi, director of the McCance Center for Brain Health at Mass General Brigham, together with Gene Bowman, the center’s clinical trials director1.
A “platform trial” tests several possible treatments at the same time, using one shared set of clinics, rules and staff instead of starting a new study for each drug1. The team plans to test 5 to 10 treatment plans, stop the ones that look weak, and move the more promising ones on to larger studies2. The design copies one used at Massachusetts General Hospital’s Healey & AMG Center to speed up the search for treatments for ALS, another brain and nerve disease1.
The University of California, San Diego, and its Alzheimer’s Disease Cooperative Study group will coordinate the clinics and standardize how data and blood samples are handled2. Up to 20 clinical sites are expected to take part2, and participants will be enrolled from across the United States1.
How the study will work
Early candidates include combinations of natural products, drugs already approved by the US Food and Drug Administration for other uses, and combinations chosen with the help of artificial intelligence2. Lab data and existing safety information will help decide which to test first2.
Volunteers will be people with no memory problems or only mild ones, whose blood tests show early stages of Alzheimer’s disease1. The main measure is p-tau217, a form of the tau protein that can be measured in blood and is linked to brain changes typical of the disease2. The team will also track other blood markers, including ones called Abeta42/Abeta40, GFAP and NfL1, which relate to amyloid plaques, inflammation and damage to nerve cells2.
The Boston Globe reported that the first five combinations will be tested in 300 patients whose blood was positive for Alzheimer’s markers, with a different combination given to each group of 60 people and another 60 people getting a placebo (a dummy treatment)3. The report does not make clear whether the placebo group is counted within the 300. According to the Globe, Tanzi said that if blood markers improve after people take the treatments, scientists will be able to tell whether the disease process is slowing3.
By the end of the four years, the researchers expect to have blood-marker and safety data for 5 to 10 treatment plans and to name candidates for larger confirming trials2.
What it does not show yet
There are no results. The award funds a study; it does not show that any drug or plant compound protects the brain.
The early tests rest on blood markers, not on memory. Mass General Brigham says treatments that show promising signals “could then advance to larger studies that measure effects on memory and daily function”1. A change in a blood protein is a hint that the disease process may be shifting; it is not the same as people keeping their memory for longer.
Tanzi explained why the team wants to start early:
“Alzheimer’s disease therapies are often evaluated too late in the disease progression, after substantial neurodegeneration has already occurred.”
He said the program aims “to start interventions earlier, identify the most promising therapies rapidly, and, ultimately, uncover strategies to prevent progression before neurodegeneration begins”1. Bowman said “one-drug-at-a-time development is slow and costly”1.
Where the candidates come from
In 2014 Tanzi’s team created what he called “Alzheimer’s in a Dish”: human brain cells grown in gel that form the plaques and tangles seen in the disease3. Tanzi told the Globe that his team used it to screen about 2,000 drugs approved for other diseases and 4,000 natural compounds from plants, then built the 5 to 10 combinations that will go into the trials3. Those screening results came from cells in a dish, not from people.
Alongside the new platform, the team will keep running a separate trial of its most promising natural product combination, called NPC11. An earlier McCance Center newsletter described NPC1 as a single-group study, where everyone gets the treatment and everyone knows it, using a 6-month regimen of two natural products, with checks on immune cells in the brain called microglia and on Alzheimer’s blood markers4.
Who is behind it, and the money involved
Tanzi has worked at Massachusetts General Hospital since 1980 and helped discover three genes that cause rare early-onset forms of Alzheimer’s3. Besides the federal award, the Globe reported that another $25 million from philanthropists will fund the four-year study3.
Tanzi also has a company interest in the field. The Globe reported that Acta Pharmaceuticals, a Boston biotech he cofounded, said it had raised $24 million to start a clinical trial of a “gamma-secretase modulator,” a type of drug Tanzi and the late Steven Wagner discovered about 25 years ago3. That early trial began this month and is recruiting 72 people3. Acta’s project is separate from the federally funded platform. Together, the efforts Tanzi leads are slated to get up to a combined $90 million from philanthropists, investors and the federal government, the Globe said3. The paper also noted that most drug trials end in failure3.
Tanzi has long described his goal as a cheap, safe “little white pill” to prevent Alzheimer’s, Endpoints News reported5. He compares the idea to taking cholesterol drugs to prevent heart disease3.
How it fits the field
Alzheimer’s affects more than 7 million Americans3. Recent drugs modestly slow the disease once symptoms appear. Leqembi, from Biogen and Eisai, was approved in 2023 for people with mild symptoms, but it costs tens of thousands of dollars a year and carries a risk of small brain bleeds3.
The new platform takes a different route: cheaper, already-available compounds, tried earlier, before memory loss, with blood tests used both to pick volunteers and to get a fast first read on whether anything is changing1. Biohack recently covered another early-prevention study, in which a transplant drug raised brain blood flow in people with an Alzheimer’s gene.
What to watch next
- Which combinations are chosen first, and when the first volunteers are enrolled.
- Results from the separate NPC1 natural-product study1.
- Whether any treatment moves p-tau217 or other blood markers, and whether those changes later show up as better memory in larger trials1.
- Progress of Acta’s early drug trial in 72 people3.
