NIH funding boosts new Alzheimer’s research on prevention, novel drug targets

$45 million in awards to test early interventions, explore new approaches including to the  Alzheimer’s Prevention Initiative APOE4 Trial  —  Drs. Eric Reiman and Pierre  Tariot, Banner Alzheimer’s Institute, Phoenix, and co-investigators. Fully  funded in fiscal 2013 at $33.2 million

Researchers  will test promising drugs aimed at preventing Alzheimer’s and identify and  validate biological targets for novel therapies, with approximately $45 million  in new funding from the National Institutes of Health. The initiative will  support innovative new studies as part of an intensified national effort to  find effective interventions for this devastating degenerative brain disease.

The  studies are among the first to be developed with direction from the 2012 NIH  Alzheimer’s Disease Research Summit: Path to Treatment and Prevention and reflect  research goals in the National Plan to Address Alzheimer’s  Disease External Web Site Policy.  Of the funding, $40 million is from an allocation from the Office of the NIH  Director, Dr. Francis Collins, with additional funding from the National  Institute on Aging (NIA), the lead Institute within NIH for Alzheimer’s  research.

“As  many as 5 million Americans face the challenge of Alzheimer’s disease, which  robs them of their memories, their independence, and ultimately, their lives,”  Dr. Collins said. “We are determined, even in a time of constrained fiscal  resources, to capitalize on exciting scientific opportunities to advance  understanding of Alzheimer’s biology and find effective therapies as quickly as  possible.”

The  clinical trials investigate possible ways to stop the progression of the  disease. The translational research study awards are focused on identifying,  characterizing and validating novel therapeutic targets.

“We  know that Alzheimer’s-related brain changes take place years, even decades,  before symptoms appear. That really may be the optimal window for drugs that  delay progression or prevent the disease altogether,” said NIA Director Dr.  Richard Hodes. “The clinical trials getting under way with these funds will  test treatments in symptom-free volunteers at risk for the disease, or those in  the very earliest stages — where we hope we can make the biggest difference.”

Basic  and genetic studies of the disease — from the abnormal proteins involved, to  genetic influences, to inflammation and other Alzheimer’s-related brain  changes — have advanced our knowledge. This has given us new insights into the  biological underpinnings of this extremely complex disorder, Dr. Hodes said.

Today’s  awards support the following clinical trials. (Individual investigators can be  contacted about when these studies will recruit participants.):

The  Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Trial  —  Dr.  Randall Bateman, Washington University, St. Louis, and co-investigators. $1.5  million in fiscal 2013, with the potential for $6 million over four years

The trial is testing new  anti-amyloid-beta drug treatments in volunteers who have an inherited form of  Alzheimer’s disease. While early-onset Alzheimer’s is rare, the knowledge  gained from this study will be highly relevant to both early- and late-onset  forms of the disease. This rare form can occur in people as early as their 30s.  Amyloid plaques in the brain are a hallmark of Alzheimer’s and are thought to  interfere with communication among brain cells, and anti-amyloid-beta therapies  attempt to treat that process. Dr. Bateman will lead a team recruiting  volunteers free of symptoms or in the earliest stages of the disorder.

The four-year trial, a multi-site  international effort, will test three anti-amyloid-beta interventions:  gantenerumab, solanezumab and a third, as yet undetermined, drug. This trial is  also supported by the Alzheimer’s Association® and the following  companies: Roche, Lilly, Avid Radiopharmaceuticals and CogState. (NIA support:  AG042791-01A1)

The  Alzheimer’s Prevention Initiative APOE4 Trial  —  Drs. Eric Reiman and Pierre  Tariot, Banner Alzheimer’s Institute, Phoenix, and co-investigators. Fully  funded in fiscal 2013 at $33.2 million

This five-year prevention trial proposes  to test an anti-amyloid drug in cognitively normal older volunteers who are at  increased risk of developing late-onset Alzheimer’s because they inherited two  copies of the APOE4 allele, the best known genetic risk for late-onset disease.  The treatment, which has not yet been selected, will be tested in this  randomized, controlled clinical trial at multiple sites. Participants will be  assessed through cognitive tests, brain imaging and cerebrospinal fluid  measurements to evaluate whether the drug impacts amyloid, other biological  measurements and the memory and thinking problems related to the disease. The  study will test the role of amyloid in the development of Alzheimer’s and will,  through imaging and biomarker techniques, help identify faster ways to evaluate  other promising prevention therapies in the future. It is anticipated that the  study will also be supported with private funding. (NIA support: AG 046150-01)

Allopregnanolone  Regenerative Therapeutic for MCI/Alzheimer’s: Dose Finding Phase 1  —  Drs.  Roberta Brinton and Lon Schneider, University of Southern California, Los  Angeles. Fully funded in fiscal 2013 at $2.4 million

This early-phase clinical trial will  evaluate over 12 weeks the safety and tolerability of increasing doses of  allopregnanolone, a natural brain steroid, in treating mild cognitive  impairment and Alzheimer’s disease. The drug has been shown to promote the  generation of new brain cells, reduce amyloid levels, and restore cognitive  function in pre-clinical animal testing. NIA has supported Dr. Brinton’s  research over many years, including basic science grants to understand  allopregnanolone’s mechanism of action in the brain, a drug development grant  which included development of optimal dose and formulation, and support for  pre-clinical toxicology studies. This support helped bring Dr. Brinton and  colleagues to the stage of being able to go into a human Phase I trial. (NIA support: AG  046148-01)

Studies  focused on the identification and validation of novel therapeutic targets for  Alzheimer’s disease include:

Pathway  Discovery, Validation and Compound Identification for Alzheimer’s Disease  — Drs.  Philip De Jager, of the Brigham and Women’s Hospital, Broad Institute, Harvard  University, Boston, and David Bennett, of Rush University Medical Center,  Chicago. $1.7 million in fiscal 2013, with the potential of $7.9 million over  five years

The study will discover, characterize  and validate complex molecular networks and candidate genes that influence  susceptibility to cognitive decline and Alzheimer’s disease. Using cutting-edge  computational methods, this multi-disciplinary team will analyze rich clinical,  pathological, genomic and other large-scale molecular data collected from over  1,000 volunteers from the Religious Order Study and the Rush Memory and Aging  Project.

Through a systems biology approach  looking at biological interactions involved in the disease, the project  ultimately seeks to identify compounds that normalize the activity of  dysfunctional nodes in molecular networks and to identify drugs for several  novel therapeutic targets. To accelerate the testing of promising therapies for  future clinical trials, the researchers will focus on drugs that have already  undergone Phase I testing in humans. (NIA support: AG 046152)

Integrative  Biology Approach to Complexity of Alzheimer’s Disease  —  Dr. Eric Schadt of  Icahn School of Medicine at Mount Sinai, New York City, and a team of  investigators. $1.6 million in fiscal 2013, with the potential of $8.2 million  over five years

This study will apply innovative analytical  methods to large-scale molecular, cellular and clinical data from Alzheimer’s  patients to construct biological network models and gain new insights into the  complex mechanisms of the disease. Several cellular and animal models will be  used to validate the actions of individual genes, as well as entire molecular  networks predicted to drive the disease. The team will also employ a  computational approach to test whether any existing drugs currently used for  other conditions are capable of modulating the Alzheimer’s networks and can,  therefore, be repurposed for Alzheimer’s treatment or prevention. (NIA support:  AG 046170-01)

A  Systems Approach to Targeting Innate Immunity in Alzheimer’s  —  Dr. Todd Golde,  University of Florida, Gainesville, and colleagues. $1.6 million in fiscal  2013, with the potential of $7.7 million over five years

This study builds on the genetic and  pathological evidence that the innate immune system, which provides immediate  defense against infection, and brain inflammation have a significant role in  Alzheimer’s disease. To identify and characterize novel therapeutic targets  within the innate immune system, this study will use a systems biology approach  to integrate genomic, gene expression, and pathological data from Alzheimer’s patients  and Alzheimer’s mouse models and analyze them in novel ways. The team will test  in animal models of the disease the validity and therapeutic potential of the  key factors predicted by the analysis. This has the potential to speed the  discovery and testing of Alzheimer’s disease prevention and treatment therapies  by targeting the immune system. (NIA support: AG 046139-01)

One  additional award made possible by this new funding is pending.

These  and other public and private activities involving Alzheimer’s disease are  taking place under the 2011 National  Alzheimer’s Project Act (PDF – 125KB) External Web Site Policy, which calls  for a stepped up national effort and coordination on research, care, and  services for Alzheimer’s and related dementias. The law mandated that the  Department of Health and Human Services establish a National Plan to  Address Alzheimer’s Disease External Web Site Policy. The initial  plan and its 2013 update call for the prevention and effective treatment of  Alzheimer’s disease by 2025. To meet the goal, one action called for was the  hosting of an Alzheimer’s  Research Summit and to move  forward with recommendations from that meeting. For more on research milestones  and progress under the plan, visit External Web Site Policy.

The  NIA leads the federal government effort conducting and supporting research on  aging and the health and well-being of older people. It provides information on  age-related cognitive change and neurodegenerative disease specifically at its  Alzheimer’s Disease Education and Referral (ADEAR) Center at For expanded  information on Alzheimer’s care and resources, please visit the federal  government’s portal website External Web Site Policy. Information on  health and on aging generally can be found at To sign up for  e-mail alerts about new findings or publications, please visit either NIA  website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

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Posted in AZBio News.