Allen Institute launches $400M Brain Health Accelerator to develop gene therapies for brain diseases

Brain mapping effort searches for roots of Parkinson's and other diseases

Allen Institute initiative aims to capture earliest cellular changes and identify new drug targets The Allen Institute, known for backing large-scale basic biology research such as ambitious "atlases" of cell types in the brain, is expanding its scope to tackle multiple neurodegenerative diseases. The Seattle-based center is already running a study of brains from Alzheimer's disease patients, but today it announced a plan to scale up its brain-mapping efforts and support the discovery of therapeutic targets across a broad range of other disorders. The 14-year, $200 million project, dubbed the Brain Health accelerator, will use a variety of molecular technologies to analyze postmortem tissue from thousands of brains from both healthy donors and those with diseases including Huntington, Parkinson's, and amyotrophic lateral sclerosis (ALS). The effort builds on the institute's ongoing Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) study, which has pinpointed cell types and neural circuits damaged even before proteins such as amyloid and tau form the abnormal brain deposits that have long defined the condition's pathology. "Most of the field, of course, focuses on the proteinopathy -- the amyloid and the tau," says Allen Institute neuroscientist Ed Lein, who is leading the new effort. Defining, and minutely mapping, affected cell types and circuits makes it possible to start to look for points for intervention, he says, some of which may be relevant across multiple diseases. Approaches like the Allen Institute's offer "foundational knowledge," says John Ngai, director of the U.S. National Institutes of Health's Brain Research through Advancing Innovative Neurotechnologies Initiative, which supports Allen Institute investigators but is not funding the new initiative directly. "We need to understand all the [brain's] cell types," he says: where they are, how they work, and how and why they start to fail. As part of the new accelerator, the institute is also creating maps of nonhuman primate brains to identify which cell types align between humans and these model species, and determine which are also analogous in mice. More precise matching of human to animal brain circuitry can help lower the risk for drug developers eager to try out drugs or gene therapies aimed at specific cell types, says Lien, who predicts the work of the consortium will lead to an in-human trial of a therapy within 5 years. The Brain Health accelerator's budget is more than double that of SEA-AD. The 28 collaborating institutions, which include universities and disease-focused nonprofits such as EverythingALS, will rely heavily on artificial intelligence to analyze the huge data sets generated by the molecular analysis of donor brain tissue. Neurologist Bradley Boeve of the Mayo Clinic, who studies frontotemporal dementia (FTD) and is not involved in the new initiative, says it's "exciting" to see the project moving forward. It "seeks to address many gaps from the cellular and circuit network perspectives" that are pertinent to diseases such as FTD, he says, "with the obvious hope that individualized treatments can advance with even greater urgency." The Allen Institute has already shown it can get provocative findings from sophisticated single-cell analyses, says Cristina Sampaio, chief medical officer for CHDI Foundation, a private research organization dedicated to Huntington that is not part of the effort but has been in discussions to join. The biggest challenge for this new project, she says, is "the human factor" -- getting a supply of human donor brains alongside detailed clinical and imaging records, and training participating institutions in new ways to preserve them for detailed analysis such as RNA sequencing, which can identify what genes were active in a cell. Ngai is optimistic that this and other brain-cell mapping initiatives will point the way to novel therapies. "We're not there yet," he says, but "we're reaching an inflection point where researchers have the potential to target just about any cell type in the brain."

Allen Institute's big new bet: $400M effort aims to go from mapping the brain to treating disease

Editor's note: This story has been updated with new figures, partners and details announced by the Allen Institute after the initiative's launch Tuesday morning. The organization that Paul Allen founded to map and understand the complexities of the human brain is now looking to turn that hard-won knowledge into treatments for brain disease. The Allen Institute is announcing Tuesday that it's launching a new initiative with $400 million in funding and the ultimate goal of developing gene therapies for neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, ALS, and Lewy body dementia. The initiative, called the Brain Health Accelerator, is a newly created unit within the Seattle-based Allen Institute, formed out of its existing Brain Science division. Starting with nearly 60 people, it's expected to expand to a 200-person effort over time. It's the first time since the institute was started in 2003 by the late Microsoft co-founder that treating disease is becoming the goal, building on its longstanding work to map the brain. The goal is "a whole new brand of therapeutics that, instead of targeting a protein, targets the cells in the circuits that are affected in disease," said Ed Lein, Allen Institute executive vice president and director of the Brain Health Accelerator, in an interview with GeekWire this week. "This could be a transformative moment for both neuroscience and how we think about treating brain diseases, because this is not what's happening now," Lein said. How it's funded: The institute says the $400 million total includes $200 million from the Fund for Science and Technology, which Allen's estate launched with a $3.1 billion endowment to support work in bioscience, the environment, and AI. After the initial announcement, the Allen Institute announced an additional $100 million from the family of Amazon founder Jeff Bezos, and $100 million more from Amazon Web Services, the NIH, and the nonprofit EverythingALS. Allen, who died in 2018, directed that proceeds from his estate go to philanthropy. His sister, Jody Allen, who chairs the foundation, is overseeing the sale of assets including his sports franchises, the Seattle Seahawks and Portland Trail Blazers, with a large portion of the proceeds expected to flow to the foundation's science and technology work. The commitment to the new Brain Health Accelerator runs over 14 years, and Lein said he expects the accelerator's total funding to grow as the initiative adds partners. It will also draw on federal funding, including grants from the National Institutes of Health. Asked about the impact of the squeeze on federal science funding, Lein described the relationship with NIH as mutually beneficial: philanthropy builds research infrastructure, federal grants help run it at scale, and the resulting data becomes a public resource. "You could call it even a public-private partnership," he said. "I wouldn't say we can't do it without them, but I would say we can't do as much without them." Going from brain maps to therapies: The initiative builds on the Allen Institute's more than two decades of work mapping the brain. Advances in single-cell genomics in recent years let researchers catalog the human brain at a resolution not previously possible, defining thousands of distinct cell types by their genes. Lein called it "the equivalent of the human genome meets Google Earth" -- a reference map that lets scientists see disease at the level of specific cells and circuits for the first time. The same map provides new opportunities to treat disease. It shows the genetic switches that turn genes on in specific cell types, which lets researchers design tools to target those cells. The potential outcome is a gene therapy that acts only on the cells a disease affects. What's ahead: The accelerator's stated goal is to reach a clinical trial within five years. Lein was careful not to say which disease might be the subject of the first trial, but acknowledged that ALS looks promising. Researchers already know which cells the disease attacks -- motor neurons in the spinal cord and cortex -- and in some cases its genetic cause. ALS also progresses quickly, which can make patients more willing to try experimental therapies. "We haven't done this before," Lein said. "We've been descriptive in our nature for our whole existence, and now we want to try to do something with that knowledge and those tools." The role of artificial intelligence: Recent advances in AI, including foundation models, give researchers new ways to find patterns and model how disease develops. "The size of the data is really going to be unlike anything we've done before, and that's incredibly well-suited to foundation modeling and new methods in AI," Lein said. Partners on the initiative include Amazon Web Services, which the Allen Institute has worked with for years. Lein said the institute is also beginning to collaborate with the Allen Institute for AI, or Ai2, the independent Seattle-based organization that Allen founded separately. The accelerator's collaborators include more than two dozen universities and research institutions, including the University of Washington, Stanford, MIT, Fred Hutch, and the patient-advocacy group EverythingALS, with international partners such as the Sanger Institute in the U.K. and Riken in Japan. Allen's legacy: Lein has been at the Allen Institute since 2004, when he joined as its first neuroscientist. He said the work is now starting to realize Allen's larger ambitions. "I feel really good, and really sad that Paul's not here to appreciate it," Lein said. "He was very curiosity-driven, but ambitious, and he hoped that we would eventually get to things that had an impact on human health. I think we're finally there."

Allen Institute's big new bet: $200M effort aims to go from mapping the brain to treating disease

The organization that Paul Allen founded to map and understand the complexities of the human brain is now looking to turn that hard-won knowledge into treatments for brain disease. The Allen Institute is announcing Tuesday that it's launching a new initiative with $200 million in initial funding and the ultimate goal of developing gene therapies for neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and ALS. The initiative, called the Brain Health Accelerator, is a newly created unit within the Seattle-based Allen Institute, formed out of its existing Brain Science division. Starting with nearly 60 people, it's expected to expand to a 200-person effort over time. It's the first time since the institute was started in 2003 by the late Microsoft co-founder that treating disease is becoming the goal, building on its longstanding work to map the brain. The goal is "a whole new brand of therapeutics that, instead of targeting a protein, targets the cells in the circuits that are affected in disease," said Ed Lein, Allen Institute executive vice president and director of the Brain Health Accelerator, in an interview with GeekWire this week. "This could be a transformative moment for both neuroscience and how we think about treating brain diseases, because this is not what's happening now," Lein said. How it's funded: The accelerator's core $200 million in funding comes from the Fund for Science and Technology, which Allen's estate launched with an initial $3.1 billion endowment to support work in bioscience, the environment, and AI. Allen, who died in 2018, directed that proceeds from his estate go to philanthropy. His sister, Jody Allen, who chairs the foundation, is overseeing the sale of assets including his sports franchises, the Seattle Seahawks and Portland Trail Blazers, with a large portion of the proceeds expected to flow to the foundation's science and technology work. The commitment to the new Brain Health Accelerator runs over 14 years, and Lein said he expects the accelerator's total funding to grow as the initiative adds partners. It will also draw on federal funding, including grants from the National Institutes of Health. Asked about the impact of the squeeze on federal science funding, Lein described the relationship with NIH as mutually beneficial: philanthropy builds research infrastructure, federal grants help run it at scale, and the resulting data becomes a public resource. "You could call it even a public-private partnership," he said. "I wouldn't say we can't do it without them, but I would say we can't do as much without them." Going from brain maps to therapies: The initiative builds on the Allen Institute's more than two decades of work mapping the brain. Advances in single-cell genomics in recent years let researchers catalog the human brain at a resolution not previously possible, defining thousands of distinct cell types by their genes. Lein called it "the equivalent of the human genome meets Google Earth" -- a reference map that lets scientists see disease at the level of specific cells and circuits for the first time. The same map provides new opportunities to treat disease. It shows the genetic switches that turn genes on in specific cell types, which lets researchers design tools to target those cells. The potential outcome is a gene therapy that acts only on the cells a disease affects. What's ahead: The accelerator's stated goal is to reach a clinical trial within five years. Lein was careful not to say which disease might be the subject of the first trial, but acknowledged that ALS looks promising. Researchers already know which cells the disease attacks -- motor neurons in the spinal cord and cortex -- and in some cases its genetic cause. ALS also progresses quickly, which can make patients more willing to try experimental therapies. "We haven't done this before," Lein said. "We've been descriptive in our nature for our whole existence, and now we want to try to do something with that knowledge and those tools." The role of artificial intelligence: Recent advances in AI, including foundation models, give researchers new ways to find patterns and model how disease develops. "The size of the data is really going to be unlike anything we've done before, and that's incredibly well-suited to foundation modeling and new methods in AI," Lein said. Partners on the initiative include Amazon Web Services, which the Allen Institute has worked with for years. Lein said the institute is also beginning to collaborate with the Allen Institute for AI, or Ai2, the independent Seattle-based organization that Allen founded separately. The accelerator's collaborators include more than two dozen universities and research institutions, including the University of Washington, Stanford, MIT, Fred Hutch, and the patient-advocacy group EverythingALS, with international partners such as the Sanger Institute in the U.K. and Riken in Japan. Allen's legacy: Lein has been at the Allen Institute since 2004, when he joined as its first neuroscientist. He said the work is now starting to realize Allen's larger ambitions. "I feel really good, and really sad that Paul's not here to appreciate it," Lein said. "He was very curiosity-driven, but ambitious, and he hoped that we would eventually get to things that had an impact on human health. I think we're finally there."