For the first time, scientists say, they have evidence that using a biologic drug to remove sticky beta amyloid plaques from the brains of people destined to develop Alzheimer\u2019s dementia can delay the disease. <\/p>\n
The researchers have been testing amyloid-removing therapies in a group of people who have rare genetic mutations that make it almost certain they\u2019ll develop Alzheimer\u2019s. <\/p>\n
The study \u2013 which is small, including just a few dozen participants \u2013 is a follow-up to a randomized-controlled trial that found no significant benefits for people who were taking one of two amyloid-lowering therapies, compared with a placebo. The extension of the study doesn\u2019t have a placebo control group and may be subject to important biases, so outside experts say the results, though striking, should be interpreted with caution. <\/p>\n
It\u2019s part of a research effort called Dominantly Inherited Alzheimer\u2019s Network, or DIAN. The study participants like to go by a different name, though. <\/p>\n
\u201cWe like to call ourselves the X-Men because we are mutants, trying to save the world from Alzheimer\u2019s disease,\u201d said Marty Reiswig <\/strong>of Denver, who has been participating in the trial since 2010. <\/p>\n The new study, published Wednesday in the journal Lancet Neurology, found that the risk of symptoms was cut in half for a small subset of 22 patients who had not shown any problems with memory or thinking and had been taking an amyloid-lowering drug called gantenerumab for an average of eight years. The results achieved statistical significance in one part of the analysis but not in others, perplexing outside experts, who struggled to make sense of the complex findings. <\/p>\n \u201cWhile this study does not conclusively prove that Alzheimer\u2019s disease onset can be delayed and uses a drug that will not likely be available, the results are scientifically promising,\u201d said Dr. Tara Spires-Jones, director of the Centre for Discovery Brain Sciences at the University of Edinburgh, in a statement to the media. She was not involved in the research. <\/p>\n The study authors believe <\/strong>that if people are started on therapy early enough and stay on it for enough time, it could forestall the development of the disease \u2014 perhaps for years. <\/p>\n It\u2019s \u201cthe first data to suggest that there\u2019s a possibility of a significant delay in the onset of progression to symptoms,\u201d said study author Dr. Eric McDade, a professor of neurology at Washington University in St. Louis. <\/p>\n McDade said this study has the longest-running data for any patients who started amyloid-lowering biologics while they were still free of symptoms. <\/p>\n \u201cWe think that there\u2019s a delay in the initial onset, maybe by years, and then within those individuals that have some mild symptoms, even the rate of progression was cut by about half,\u201d he said. <\/p>\n The achievement of this long-hoped-for result comes with optimism but also panic, however. <\/p>\n The research team says the meetings to review their National Institutes of Health grant funding have been canceled twice. Their grant has to be reviewed before they can be referred to what\u2019s known as a council meeting, where funding decisions are made. If their grant misses a <\/strong>council meeting in May, the money for the study, which has been going since 2008, could run out. <\/p>\n \u201cIt ends up becoming a really difficult position we\u2019re in and that the participants are in,\u201d McDade said. <\/p>\n Patients could lose access to the study drugs, especially if they\u2019re in countries where the medications haven\u2019t been approved. If people can\u2019t stay on the drugs, researchers may never find out how durable the benefit may be or be able to answer critical questions like for whom the medications work best. <\/p>\n Keeping that group that has been on the amyloid drugs the longest is \u201cabsolutely critical,\u201d McDade said. <\/p>\n In the 1980s, researchers studying the autopsied brains of people with Alzheimer\u2019s discovered that they were clogged with sticky plaques made from beta amyloid proteins and toxic tangles made of a protein called tau. They theorized that removing these proteins from the brain might delay or even reverse the disease, and they began to hunt for therapies that could do that. <\/p>\n For decades, scientists have been testing a range of biologic medications that recognize and remove beta amyloid proteins, with mostly lackluster results. <\/p>\n In late-stage clinical trials involving more than 1,800 people with early Alzheimer\u2019s disease, one of these drugs, gantenerumab, slowed the progression of symptoms compared with a placebo, but it wasn\u2019t a big enough benefit to pass a test of statistical significance, meaning the result could have been due to chance alone. It was considered a failed drug. <\/p>\n Meanwhile, two similar drugs \u2014 lecanemab, or Leqembi, and donanemab, or Kisunla \u2014 did meet the US Food and Drug Administration\u2019s bar and were approved to treat people with Alzheimer\u2019s who have mild symptoms. <\/p>\n Both therapies are expensive, may cause brain swelling and, in clinical trials, delayed the progression of symptoms by months compared with placebos. The modest benefits mean some doctors and patients to shy away from using them. <\/p>\n Researchers testing gantenerumab in people with gene mutations that set them up for Alzheimer\u2019s in the DIAN got permission from the FDA to continue using the drug for as long as possible. When they couldn\u2019t keep the participants on gantenerumab any longer, they switched them to its sister drug lecanemab. <\/p>\n Sue, a study participant in Texas, has been in the gantenerumab arm of the trial since 2012. She joined the study shortly after she found out that she and three of her five siblings <\/strong>had a gene mutation that made it almost certain they would develop early-onset Alzheimer\u2019s disease. <\/p>\n Of six children in her family, two brothers and two sisters have the mutation. One brother was tested but doesn\u2019t have it, and another brother doesn\u2019t want to be tested but remains free of symptoms. Two of her brothers and a sister developed symptoms around age 57. Sue, who at 61 is the youngest of her siblings, <\/strong>has not. <\/p>\n \u201cI\u2019m fine. I\u2019m totally fine,\u201d said Sue, who asked to be be identified only by her first name to protect family members who may also have the mutation. <\/p>\n Her brothers, who were also in the trial but began taking the medication after they had developed symptoms, didn\u2019t benefit as much. <\/p>\n When she started the study 13 <\/strong>years ago, she hoped she would contribute to scientific understanding of the disease. She has had 40 MRIs, 30 PET scans and more than a dozen lumbar punctures to collect her spinal fluid. <\/p>\n Tests show that her brain and her thinking are normal. She gets \u201cqueen bee,\u201d <\/strong>the top daily ranking, <\/strong>on the New York Times Spelling Bee game every day. <\/p>\n \u201cI still feel like, fundamentally, I\u2019m doing it to help the science, but at this point, it\u2019s helping me,\u201d she said. \u201cI truly believe that.\u201d <\/p>\n Sue believes the drugs have held off the disease for about four years for her. When the disease runs in families this way, she believes, there\u2019s a pretty clear age when people start to decline, and she thinks the medication has pushed that back. <\/p>\n After watching her brothers begin to decline, she worked with a financial planner to save as much money as possible and planned for an early retirement. Today, she\u2019s still working part-time. <\/p>\n For the study, the researchers recruited DIAN members who were cognitively normal or who had only mild symptoms, and who were in a window of time spanning 15 years before to 10 years after their estimated age of diagnosis. The researchers estimated the potential age at diagnosis by looking at the ages when other family members began showing symptoms. <\/p>\n For the first phase of the study, participants were randomly assigned to take either gantenerumab, another amyloid-lowering drug called solanezumab or a placebo. That study ran from the end of 2012 to the beginning of 2019. <\/p>\n At the end of that study, researchers allowed participants who had finished it to continue on gantenerumab in increasing doses for three years. That extension ran at 18 clinical trial sites in seven countries. In 2023, the drug\u2019s sponsor, Roche, discontinued development of gantenerumab after disappointing study results made it unlikely to be approved by the FDA. <\/p>\n The study released Wednesday reports the results of this extension, in which all the participants \u2013 73 \u2013 who continued on the therapy knew that they were on the drug. <\/p>\n Study participants who took gantenerumab during either the double-blind, placebo-controlled portion of the study or only in the open extension had a modest benefit. Their odds of developing symptoms were cut by about 20%, but the result was not statistically significant. <\/p>\n For the 22 people who had been on gantenerumab the longest \u2013 an average of eight years \u2013 the benefit was larger and at least partly statistically significant. The drug cut their risk of symptoms by almost half compared with people who were in an observational arm of the study, in which researchers were monitoring the progress of participants but not treating them. <\/p>\n Reiswig, like many members of his family, carries a mutation in a gene called presenilin-2, which causes his brain to overproduce amyloid plaques. His relatives who carry the mutation begin showing Alzheimer\u2019s symptoms between ages 47 and 50. Reiswig is 46. <\/p>\n \u201cI\u2019m staring the gun right down the barrel,\u201d he said. <\/p>\n His father also participated in DIAN in the observational arm but didn\u2019t start the drug trial because he thought he was too sick to get any benefit. He died of Alzheimer\u2019s in 2019, at the age of 66. <\/p>\n \u201cThat\u2019s old for our family,\u201d Reiswig said. <\/p>\n For years, Reiswig resisted finding out whether he carried the mutation, but he did get tested in 2020. When he learned that he had it, \u201cI punched pillows, and I cried really hard,\u201d Reiswig said. \u201cIt was the worst day ever.\u201d <\/p>\n But \u201ceventually, you run out of tears,\u201d he said. He and his wife decided \u201cwe\u2019re just going to get busy living,\u201d because he didn\u2019t know how many good years he might have after the age of 47. <\/p>\n Reiswig started in the solanezumab arm of the study and switched to gantenerumab in the extension. <\/p>\n He hasn\u2019t seen any symptoms, but he also doesn\u2019t know whether he\u2019s actually getting any benefit from the drug. <\/p>\n Researchers who were not involved in the study said that even though it was small and not placebo-controlled, and the data is preliminary, it\u2019s worth paying attention to. <\/p>\n \u201cIn the context of all we have learned about the value of amyloid removal in sporadic AD, these data are encouraging,\u201d Dr. Paul Aisen, director of the Alzheimer\u2019s Therapeutic Research Institute at the University of Southern California, wrote in an email. <\/p>\n Aisen led a study that tested solanezumab in people who had amyloid in their brains but didn\u2019t have any symptoms. That study found no benefit to taking the drug, compared with a placebo, after more than four years of treatment. <\/p>\n Aisen believes that his study was negative because it tested a first-generation drug that didn\u2019t remove amyloid as strongly as some of the newer ones do. <\/p>\n He\u2019s now leading another study testing lecanemab in patients who don\u2019t have symptoms. Because a long treatment period is required to see results in this stage of the disease, Aisen says they won\u2019t have results until 2028 or 2029. <\/p>\n \u201cMuch more needs to be done, and additional major studies are in progress,\u201d he wrote. <\/p>\n Others said the results from the latest research were hard to interpret, given the biases that probably exist in the study population. <\/p>\n \u201cI don\u2019t think there\u2019s a clear signal here that this is working,\u201d said Dr. Michael Greicius, a professor of neurology and neurological sciences at Stanford University who was not involved in the study. <\/p>\n Grecius said it\u2019s difficult to compare this group of 22 people who continued on gantenerumab to people in the observational study, because people in the extension were able to join only if they finished the placebo-controlled trial. People who dropped out of the phase 3 study weren\u2019t eligible to participate, which means participants in the extension had to be relatively healthy and doing better in the first place. <\/p>\n \u201cThese are big caveats,\u201d Greicius said. <\/p>\n He says the biomarker data included in the paper shows that as the researchers increased the drug dosage, they were able to remove more amyloid from the brain. <\/p>\n But other biomarker data is less clear. PET imaging scans, for example, didn\u2019t show much of a difference in the amounts of tau protein in the brain, even after extended treatment. <\/p>\n If there is a real effect here, Greicius says, it\u2019s not likely to be a permanent one. \u201cPeople are still progressing. They\u2019re progressing more slowly than the control group.\u201d <\/p>\n Even though this data comes with a lot of uncertainty \u2013 or perhaps because it comes with so much uncertainty \u2013 Greicius says it\u2019s even more important to continue the research. <\/p>\n \u201cThis is an invaluable study population,\u201d he said. \u201cContinuing to follow them on treatment may provide the best test of the amyloid hypothesis that the field can undertake and stands to provide critical evidence either for or against it. This should be highly prioritized for continued funding.\u201d <\/p>\n Reiswig said it would be devastating if the study had to be stopped due to lack of funding. <\/p>\n \u201cPersonally, I\u2019m terrified of that. I\u2019ll be taken off of a life-saving drug and left to wait until symptoms begin to begin slowing the disease with Kisunla or Leqembi,\u201d he said. <\/p>\n He says he and the other DIAN participants have given decades of their lives to research, to developing a treatment, but then could be denied treatments they helped to test. <\/p>\n \u201cHonestly, that feels criminal to me,\u201d he said. \u201cWe are so close to preventing the world\u2019s most tragic and expensive disease.\u201d <\/p>\n<\/p>\n <\/p>\n","protected":false},"excerpt":{"rendered":" For the first time, scientists say, they have evidence that using a biologic drug to…<\/p>\n","protected":false},"author":1,"featured_media":2920,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"class_list":["post-2919","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-news"],"_links":{"self":[{"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/posts\/2919","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/comments?post=2919"}],"version-history":[{"count":0,"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/posts\/2919\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/media\/2920"}],"wp:attachment":[{"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/media?parent=2919"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/categories?post=2919"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthyretirementnews.com\/index.php\/wp-json\/wp\/v2\/tags?post=2919"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}} Long-running studies begin to bear fruit<\/h2>\n
Glimmers of hope<\/h2>\n
More research is needed<\/h2>\n