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ST. LOUIS — In 2012, researchers at Washington University started a study of patients with rare genetic mutations in their families that almost certainly cause Alzheimer’s disease at a devastatingly early age — in their 30s, 40s and 50s.

The study set out to determine if taking medications targeting plaques that build up in the brain years before symptoms begin could save their lives, and perhaps the lives of others who sporadically get Alzheimer’s later in life.

For the first time, results show it’s possible.

A shows that a small number of the participants — those who had no cognitive problems at the study’s start and who received the drug the longest — experienced a significant delay in the onset of symptoms.

These 22 participants who had received the drug for an average of eight years showed a 50% reduction in progression, which means five to 15 years of dementia-free life — a number that can potentially increase if they continue the medication.

“This is the first clinical trial to have evidence that Alzheimer’s disease symptoms can be delayed, it can be prevented,� said Washington University neurologist , director of the research. “For us that is quite incredible, but for the families this is lifesaving.�

However, the ability to continue the research — so participants can continue taking the medications that may be keeping symptoms at bay, and scientists can find more definitive answers — is under threat because of slowdowns and uncertainties at the federal National Institutes of Health.

Like most studies in the U.S., the research relies on grants from the NIH. With an annual budget of nearly $48 billion, NIH is the largest public funder of biomedical research in the world.

Immediately after President Donald Trump took office, his administration imposed a “communications pause� on federal agencies in order to make sure actions align with the administration’s ideological and cost-saving goals.

The pause prevented the NIH from posting notices of grant-review meetings to the , a required step before the critical meetings that decide funding can be held. Only some notices have slowly resumed.

The result has been scores of canceled meetings and uncertainty over if and when they will be rescheduled. that about 16,000 grant applications vying for around $1.5 billion in NIH funding have stalled.

Bateman said the NIH last year accepted his grant application to continue the drug study for another five years. But a review committee meeting that was supposed to be held at the end of January was canceled, he said. It was rescheduled for March, but that was canceled too. It’s unknown for certain if one will be held.

“We’ve been asking,� Bateman said. “Communication is challenging because a lot of times we don’t get direct responses back.�

The review committee meeting is required before a council meets to decide final approval, typically in May. Scientists don’t know what will happen if review meetings aren’t held by then.

Bateman said, “I’ve never seen anything like this happen at the NIH before in the 25 years I’ve been doing research,� Bateman said.

Need for continuity

This type of long-term study into a progressive disease cannot stop and resume later.

“A trial like this — when treating individuals that have been treated for the past 10 years and you want to continue treatment to demonstrate the benefit — if you stop you won’t know the benefit,� Bateman said. “Any future information or future answers will be lost permanently.�

NIH funding helped Washington University in 2008 launch the effort to study families plagued with these rare genetic mutations — called the — knowing the families could provide important clues about the disease.

The network has grown to over 40 study sites , which have helped recruit and gather information on over 1,000 participants.

With the help of over $200 million in NIH funding since, the study network has led to key discoveries for all Alzheimer’s patients such as: the plaques — made up of proteins called amyloid betas — begin growing as long as 20 years before dementia symptoms, these plaques cause other brain changes that lead to memory loss, and the creation of a blood test that can detect the start of these changes.

Bateman believes that continuing the decadelong research of plaque-targeting drugs for another five years could lead to a huge payoff — the ability to test all adults for their risk of Alzheimer’s disease and intervene to delay the onset of the disease by several years and maybe even prevent it altogether.

“To drop the ball at the very last play, quarter or inning or whatever sports analogy you want to use, is devastating,� he said. “It’s almost unthinkable that after so much investment and success and where we are at this moment, that we wouldn’t continue, that we would have to shut everything down.�

Study participants

Marty Reiswig, 46, of the Denver area, remembers going to a family reunion when he was in college and practically everyone over age 50 had dementia.

Reiswig’s dad began getting sick in his early 50s, slowly becoming a shell of a person until dying at age 66. His dad’s cousins got sick and died at even earlier ages.

Reiswig’s brother underwent genetic testing and discovered he did not carry the high-risk Alzheimer’s mutation, but Reiswig didn’t want to find out.

Reiswig joined the Dominantly Inherited Alzheimer’s Network around 2010 and enrolled in the drug study when it launched at the end of 2012, which participants could do without knowing their genetic status.

In 2020, one of the plaque-removing drugs used in the study, gatenenerumab, emerged as a promising treatment. Researchers won approval to extend giving gatenenerumab in higher doses to all the study participants, including those in the placebo group.

But to continue in the study, participants had to know whether they had the genetic mutation. In August 2020, Reiswig learned he tested positive, practically guaranteeing he would get Alzheimer’s just like his other family members.

“I knew, even more horrifyingly, that I had two children in their teens who were now at 50% risk of getting the gene mutations,� Reiswig said. “That is a horrible part of it.�

For the next nearly three years, participants in the extension group were compared to those in DIAN who chose not to participate in drug studies or who were in the placebo group and did not continue into the extension.

Analysis of the data revealed the findings published Wednesday — the drug cuts the risk of developing symptoms in half, but only for those who started with no symptoms and were treated with the drug the longest.

Reiswig doesn’t know for certain if he is in that group, as he doesn’t know if he first received a placebo or another type of drug. He is also among some extension participants who haven’t quite reached their typical age of onset of symptoms, which is why continuing the drug research is important.

“I have every scientific reason to believe that if I were allowed to stay on (a plaque-targeting drug), that I would be able to survive Alzheimer’s,� he said, “that I would be one of first people on the planet to be an Alzheimer’s survivor.�

Emotionally, he said, the possibility of not being able to continue taking the drug is terrifying for him and his family.

“I don’t want anyone else to get Alzheimer’s disease,� he said. “It’s horrible … in my humble opinion, it has to be one of the worst ways to die for you and your loved ones.�

The study participants have invested months in their expected short lives, getting monthly injections or IV infusions of drugs, a quarterly MRI to catch any brain bleeding (a side effect of the drugs), plus traveling to a study site for annual brain scans, spinal taps, blood draws, and cognitive and clinical evaluations.

Sue, a study participant from Austin who did not want her last name used to protect the identity of other family members, said she felt a “moral obligation to make good of the bad cards I was dealt.� She joined the drug trial in 2015.

Married and a stepmom, Sue is now 61 and has no dementia symptoms despite having the gene. Two of her older brothers and an older sister began having symptoms at ages 57 and 58. Her brothers died at ages 65 and 66. Her sister is 63 and homebound.

Sue’s teen nieces and nephews look to her as a sign of hope that they’ll be OK. She’s starting to look somewhat long-term at her retirement life.

She says she can’t let herself think about the possibility of not having enough funding to continue the research. Two similar drugs to gantenerumab were recently approved by the FDA, but only for patients who already have symptoms.

“We finally found this class of drugs works or seems to work,� she said, “now is not the time to be putting the brakes on it.�

‘Funding is critical’

The company that makes gantenerumab discontinued the drug in mid-2023, just shy of the end of the three-year extension study to focus on developing a newer version, Bateman said.

to one of the FDA-approved drugs, lecanemab, which participants have been taking ever since thanks to , the drugmaker and other philanthropic donors.

That funding will last another six months or so, Bateman said. Researchers had been hopeful that a new NIH grant would allow the study to continue for another five years, until all the participants are at or well beyond their typical age of onset.

“We think this the evidence needed to prove beyond a doubt that we can delay the onset of Alzheimer’s,� Bateman said, as well as determine how soon patients need to be treated with plaque-removing drugs in order to see a substantial benefit.

“If we don’t get the grant,� Bateman said, “then obviously the study has to stop, and all these patients lose access to the drugs and treatment.�

Washington University is also leading another NIH-funded study that started last month, the , which involves DIAN families and the investigational amyloid-removing drug remternetug. Uncertainties at the NIH threaten that study as well.

The prevention trial has enrolled 60 participants as young as 18, up to 25 years before the onset of dementia symptoms, to determine whether early drug intervention can prevent any signs of the disease, said lead researcher Dr. Eric McDade. And more are waiting to enroll.

McDade said the NIH meetings necessary to renew the funding were supposed to be held in February but got postponed to April.

“In order to complete the study, that NIH funding is critical,� he said. “It’s the largest proportion of the overall funding to go towards getting this trial across the finish line.�

Reiswig said he feels certain that scientists are on the cusp of preventing Alzheimer’s disease not just in his family but for the millions across the world.

“It’s really scary for me to think that all of that fuel, all of that progress we have made could stop suddenly,� he said, “and we could crash the plane when we already have our landing gear out.�