Our Portfolio

The Alzheimer's Drug Discovery Foundation (ADDF) publishes all programs that we fund in our research portfolio. Funded research projects can be viewed by the year of funding or by program area, and can also be found by searching for an investigator or certain keywords. Please note that your search term(s) must contain at least four characters.

Additionally, please note that grant funding priorities at the ADDF change over time. The ADDF maintains strict confidentiality with all of our funded projects and cannot share additional information on projects without permission from the investigator(s).

The ADDF does not recommend one particular clinical trial or research program over another. The ADDF is not responsible for the accuracy of the information provided, the selection of research subjects (patients) or the conduct of the clinical trial, treatment IND/expanded access program or other research program.

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- Year
- Grantee
- Organization
- Title
- Program Area
- Amount

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- 2019
- Kejal Kantarci, MD, MS
- Mayo Clinic
- Effects of Early Menopausal Hormone Therapy on Imaging Biomarkers of Cognitive Health
- Prevention
- $66,094
Duration: 01/01/2019 - 01/01/2021

Abstract:

Many studies have reported that use of menopausal hormone therapy is associated with lower risk of dementia and cognitive decline. However, clinical findings have been mixed and suggest that neuroprotective benefit of hormone therapy may depend on many factors such as the timing of treatment and the type of hormone therapy. Dr. Kantarci will be performing a 12-year follow up of the Kronos Early Estrogen Prevention Study (KEEPS), a nationwide clinical trial that tested two different menopausal hormone therapies in newly postmenopausal women. Dr. Kantarci’s objective is to assess the long-term benefits and risks of these menopausal hormone therapies on amyloid (Alzheimer's disease marker), heart disease and stroke risk, cognitive function, and mood health. This $10M follow-up study funded by the National Institute on Aging provides a unique and special opportunity to clarify the long-term effects of menopausal hormone therapies on cognitive health and Alzheimer’s risk based on a high quality clinical trial initiated 12 years ago. Add-on funding from ADDF will support brain imaging of another Alzheimer’s disease marker tau. Findings from this study will inform whether postmenopausal women should be taking hormone replacement therapy and which kind is most protective for brain health.

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- 2018
- Phillip Tully, PhD, MPsych (clin), B.H.Sc
- University of Adelaide
- Minimizing Blood Pressure Variability with Antihypertensive Drugs to Reduce Dementia Risk
- Prevention
- $99,363
Duration: 10/01/2018 - 10/01/2020

Abstract:

Elevated blood pressure in mid-life is a modifiable risk factor for cerebrovascular and Alzheimer’s disease. However, recent studies have indicated that intra-individual fluctuations in blood pressure, or blood pressure-variability, may be more important than mean blood pressure, per se, in predicting future risk of cerebrovascular disease. Importantly, certain blood pressure medications may better control blood pressure-variability than others. Dr. Tully will make use of ADDF’s Consortium of Cohorts for Alzheimer’s Prevention Action (CAPA) to pool together individuals from 10 cohorts with over 50,000 patients to study whether certain classes of anti-hypertensive drugs are better able to control blood pressure-variability and whether these drugs also reduce the risk of dementia later in life. The cohorts Dr. Tully has access to contain data for cognitive function, dementia status, and imaging data. Findings from this study will determine whether certain classes of anti-hypertensives are better able to reduce blood pressure-variability, cerebrovascular disease, and dementia risk. This will allow doctors to prescribe anti-hypertensives that will most reduce Alzheimer’s risk later in life.

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- 2018
- Michela Gallagher, PhD
- AgeneBio, Inc.
- 4th An. Goodes Prize for Excellence in AD Drug Discovery: Imaging Sub-Study, HOPE4MCI Phase 3 Trial
- Clinical
- $150,000
Duration: 09/01/2018 - 08/31/2019

Abstract:

People with amnestic mild cognitive impairment (aMCI) have more memory problems than expected for their age. While their symptoms are not as severe as patients with Alzheimer’s, they are at increased risk for developing the dementia. Dr. Gallagher’s research at Johns Hopkins provided the first scientific evidence for developing therapies that target hyperactivity in brain cells, especially in aMCI patients when hyperactivity is most pronounced. Dr. Gallagher founded AgeneBio to tackle hyperactivity in aMCI patients using a low dose formulation of the currently FDA-approved epilepsy drug levetiracetam. Hence, this is a program that is repurposing an existing drug with a novel formulation. HOPE4MCI, a pivotal Phase 3 clinical trial with their drug, is currently underway. The program has been supported by ADDF for several years. With funds from the ADDF Goodes Prize, Dr. Gallagher will acquire a novel set of imaging data using high resolution MRI and tau PET scans. These data will provide sensitive and quantitative measures for the HOPE4MCI trial and will determine if lowering hyperactivity slows the spread of tau protein.

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- 2018
- Paul Worley, MD
- Johns Hopkins School of Medicine
- Resilience Biomarker NPTX2 and Alzheimer's Disease Progression
- Prevention, CSF
- $160,000
Duration: 07/15/2018 - 07/14/2019

Abstract:

Dr. Paul Worley and his team have identified a novel biomarker, termed NPTX2, that may be able to identify patients at risk for cognitive decline. This biomarker distinguishes human subjects with mild cognitive impairment (MCI) or Alzheimer's disease from similarly aged people with normal cognition. NPTX2 is found in the synapses, or neural connections, of brain centers involved in memory. Through a previous ADDF-funded project, Dr. Worley's collaborator, Douglas Galasko developed an assay that can detect NPTX2 in cerebrospinal fluid (CSF) from spinal taps. They showed that MCI and Alzheimer's patients had lower NPTX2 levels in CSF than healthy subjects. In this project, Dr. Worley will test a larger cohort of MCI and Alzheimer's patients and assess NPTX2 levels in CSF samples from patients with other age-related types of dementia. These studies will validate the use of measuring NPTX2 in CSF as a diagnostic tool and biomarker of disease progression in Alzheimer's disease.

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- 2018
- Paula Grammas, PhD
- University of Rhode Island
- Vascular Activation: A Novel Therapeutic Target for Alzheimer's Disease
- Clinical
- $1,294,881
Duration: 08/06/2018 - 08/06/2021

Abstract:

BEACON is the first clinical study to look into the possible role of the brain's blood vessels in Alzheimer's disease. Extensive research has shown that factors, such as high blood pressure, diabetes, and stroke, injure blood vessels in the brain. This can lead to inflammation that can cause damage or death of brain cells that occurs in Alzheimer's disease. The BEACON Study, based on 30 years of research by Dr. Grammas and her team, repurposes an existing FDA-approved drug, dabigatran, to suppress one part of this inflammation process. They were the first to identify an inflammatory cascade in which injury to the cells lining blood vessels in the brain (known as endothelial cells) "activates" them, causing the release of different molecules harmful or toxic to nerve cells. The one-year trial will test safety and tolerability in Alzheimer’s patients and will measure biomarkers that can provide information on if and how the treatment is affecting disease. If successful, this study could lead to phase 2 clinical trials of dabigatran in Alzheimer's. Results are expected in late 2020.

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- 2018
- Manfred Windisch, PhD
- NeuroKine Therapeutics
- Phase 1 Clinical Trial of a Novel Stress Kinase Inhibitor
- Clinical
- $860,500
Duration: 08/01/2018 - 08/01/2019

Abstract:

Neuroinflammation and the loss of connections between brain cells are hallmarks of most neurodegenerative diseases, including Alzheimer's. MW150, developed by the ADDF's 2016 Goode's Prize winner Dr. Martin Watterson, is a novel therapeutic that targets both of these pathologies. ADDF support of phase 1 studies will make MW150 the first drug in its class to be tested in humans. These first-in-human studies will allow the team at NeuroKine to assess the safety and tolerability of MW150 and gather information on where the drug accumulates in the body. The team will also perform some preliminary analyses on samples from the patients to assess if and how the drug is hitting its intended target. With the successful completion of these experiments, MW150 will be poised to move into larger phase 2 trials.

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- 2018
- Ronald Crystal, MD
- Weill Medical College of Cornell University
- Phase I Study of an AAVrh.10-Mediated Apolipoprotein E2 Gene Delivery to the CNS for the Treatment o
- Clinical
- $3,006,472
Duration: 02/01/2018 – 02/01/2021

Abstract:

Alzheimer's disease affects 5 million Americans and is increasing in prevalence and economic impact. Existing drugs do little to limit the disease process and no preventive therapies are known. It is known that inheritance of variant APOE4 conveys high risk for development of early-onset Alzheimer's, and that inheritance of APOE2 is protective. Based on our data that gene transfer of the APOE2 coding sequence to the CNS of murine models of Alzheimer's suppresses amyloid burden in the CNS and that we can get widespread expression of APOE2 in a safe manner in the much larger brain of a nonhuman primate, we propose a program with rapid translation to the clinic of adeno-associated virus (AAV)-mediated CNS transfer of the human APOE2 coding sequence to prevent the development and/or progression of Alzheimer's disease. Our proposed program has been formulated with input received from the Food and Drug Administration following a pre-Investigational New Drug Application meeting that we had with them and the project progress meeting with the team at ADDF (April 21, 2017). This proposal has three primary objectives; (1) investigational new drug submission to the FDA and other regulatory bodies and gaining approvals needed to initiate a phase I clinical study; (2) production, purification, and characterization of AAVrh.10hAPOE2 for a phase 1 clinical study with the required lot release testing and stability studies; and (3) to carry out a Phase I clinical trial with n=15 subjects that are APOE4 homozygotes who have mild cognitive decline or early dementia, testing the safety and preliminary efficacy of intracisternal delivery of AAVrh.10hAPOE2 to the CNS. The proposal will be carried out at Weill Cornell Medical College (WCMC) under the co-principal investigator leadership of Ronald Crystal, Chair, Department of Genetic Medicine and Gregory Petsko, Director, Appel Alzheimer's Disease Institute.

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- 2018
- Miles Berger, MD, PhD
- Duke University Medical Center
- APOE Mimetic Drug CN-105 to Reduce Postoperative Delirium and Cognitive Dysfunction after Non-Cardia
- Clinical
- $1,631,197
Duration: 07/15/2018 - 07/15/2021

Abstract:

Postoperative cognitive dysfunction (POCD) and delirium occur in up to 40% of Americans over age 65 who undergo anesthesia and non-cardiac surgery each year. This is associated with decreased quality of life, increased mortality, and a possible increased dementia risk. These conditions may be caused by brain inflammation and exacerbated by pre-existing Alzheimer's disease. With prior ADDF funding, the investigators developed CN-105, a peptide that mimics the naturally occurring protein, APOE. CN-105 blocks brain damage from Alzheimer's disease and inflammation in preclinical tests. A phase 1 clinical trial showed the drug is safe in humans. With this round of ADDF funding, Dr. Berger will conduct a Phase 2 clinical trial to test whether CN-105 reduces POCD and delirium rates in older orthopedic surgery patients. The trial will also assess if CN-105 can reverse brain inflammation associated with POCD and delirium.

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- 2018
- Janice Kranz, PhD
- Eikonizo Therapeutics, Inc.
- De-Risking an HDAC6 Inhibitor for Neurodegenerative Tauopathies
- Clinical
- $841,062
Duration: 04/01/2018 - 03/31/2019

Abstract:

Tauopathies, which include Alzheimer's disease and frontotemporal degeneration, are a class of neurodegenerative diseases caused by the abnormal accumulation of tau protein in the brain. HDAC6, an enzyme that is elevated in the brains of Alzheimer's patients, may play a central role in modifying several proteins involved in neurodegenerative diseases, including tau. Eikonizo Therapeutics is developing a novel HDAC6 inhibitor that was previously shown to prevent tau accumulation in preclinical studies. The current ADDF funding will evaluate the highly selective HDAC6 inhibitor in humans. The team has successfully added a radiolabel to their drug that will allow them to visualize it in the brain through PET imaging. This pivotal study will establish HDAC6 as a therapeutic target in humans and de-risk the clinical development of their drug.

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- 2018
- Bruno Vellas, MD
- Gerontopole, CHU Toulouse
- Prevention of Cognitive Decline in Older Adults with Low DHA/EPA Index in Red Blood Cells
- $300,000
Duration: 04/01/2017 - 04/01/2022

Abstract:

Decades of research have suggested that omega-3 fatty acids, like DHA and EPA, may prevent cognitive decline. Levels of DHA, one of the brain's essential building blocks, are lower in brain regions associated with Alzheimer's disease. Large clinical trials have highlighted the role of omega-3 in preventing cognitive decline, particularly in patients with low levels of omega-3 in the blood. However, these trials ultimately yielded mixed results. ADDF is providing funding for a pivotal Phase 3 trial, where Dr. Vellas and his team will evaluate whether omega-3 fatty acid supplementation can prevent cognitive decline in older adults with low omega-3 blood levels. Omega-3 treatment may provide a cost-effective therapy that is well-tolerated and without any severe known side effects. If successful, simple blood tests could be used to guide the use of omega-3 fatty acids to prevent cognitive decline in high risk individuals.

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