Alzheimer's Disease Therapeutics Accelerator Projects

The IOA's first round of funded Alzheimer's Disease Therapeutics Accelerator Projects have been announced! 

View the funded projects here. 

The University of Pennsylvania Institute on Aging (IOA) is pleased to announce a Letter of Intent (LOI) request for collaborative projects that focus on developing next-generation therapies for Alzheimer’s disease (AD). These projects will be supported by a research grant obtained by the co-Directors of the IOA from the Delaware Community Foundation.

Alzheimer's Disease Therapeutics Accelerator Projects


This award will support projects that focus on AD therapeutics including projects that address comorbid pathologies in the setting of Alzheimer’s disease. Both basic science and translational projects are eligible. However, basic science projects will only be considered if they focus on therapeutic development; projects that focus on mechanisms of disease without work towards a therapeutic will not be supported. Biomarker projects will be considered only if they describe evidence that they are directly related to enhancing existing or novel therapeutics.

Leaders for these proposed projects may reside in any of Penn’s 12 schools and priority will be given to projects that work across labs. Applicants are strongly encouraged to include a patient-facing clinical researcher to enhance the likelihood of future translation. Applicants who are IOA members will receive special preference and all applicants are encouraged to become members. Select teams of investigators will work collaboratively with the IOA to further develop their project(s).


Each project may request funds for up to $250,000 in total costs (direct costs will be $227,300 after a 10% indirect cost is applied). We anticipate that funds will be used over 1 to 2 years. Exceptional projects may request additional funding after the initial funds have been spent. Salary support for Project Leaders should be commensurate with their effort needed to execute the project.

Application Process

Letters of Intent (LOI) can be up to 1 page long and must include:

  1. Name(s) of the Project Leader(s) with contact information (including email address)
  2. Title of proposed project
  3. Overarching goal of project
  4. Abstract OR one paragraph description of the project
  5. Explanation of the project’s potential to result in or enhance AD therapeutics

LOIs will be accepted on a rolling basis and must be emailed to Kathy Jedrziewski, IOA Deputy Director at We anticipate funding several projects through 2027.

For more information, contact Kathy Jedrziewski,

Download the full LOI request here.


Funded Projects

Principal Investigators: Christopher Brown, MD, PhD, Dawn Mechanic-Hamilton, PhD, ABPP/CN, and David Wolk, MD

The goal of this study is to provide personalized monitoring of beneficial and adverse treatment response in individuals receiving anti-amyloid therapies for early Alzheimer’s disease. Investigators hope to discover which neuroimaging, blood-based, and cognitive measures best predict beneficial outcomes after treatment and which measures predict development of adverse outcomes.

Results of this study could be used to help guide decisions around treatment cessation and continuation, provide personalized safety monitoring that is less burdensome than current requirements, and identify mechanisms that may help enhance beneficial effects and/or reduce adverse side effects of anti-amyloid therapy.

“This is the first study to examine detailed imaging and cognitive measures longitudinally and explore individual differences in treatment response to anti-amyloid therapies,” said Christopher Brown, MD, instructor of Neurology at the University of Pennsylvania and principal investigator of the study. “Prior studies have been limited to looking at group effects that are not easy to translate to the individual patient level in the clinic.”

Principal Investigators: Zissimos Mourelatos, MD, Kelvin Luk, PhD, and Virginia M.-Y. Lee, PhD

The overarching goal of this project is to develop novel RNA therapeutics for the major human neurodegenerative diseases such as Alzheimer’s Disease (AD) and Related Dementias, Parkinson’s Disease (PD) and related Synucleinopathies.

Deposition of various combinations of pathogenic proteins is commonly seen in neurodegeneration. A promising therapeutic strategy is to reduce the levels of proteins that aggregate in neurodegenerative diseases by targeting their mRNAs.

“We developed a new platform for potent, in vivo gene silencing based on bitargeting linked small interfering RNAs (BlisRNAs) that can simultaneously silence two genes,” said principal investigator Zissimos Mourelatos, MD, Professor of Pathology and Laboratory Medicine. “BlisRNAs are simple and economical to synthesize and compatible with automated, large-scale production.”

So far, Dr. Mourelatos and his team have developed potent BlisRNAs that silence Microtubule-associated protein tau (MAPT), amyloid precursor protein (APP) and Synuclein Alpha (SNCA).

They are conducting biodistribution, safety, and efficacy studies of their BlisRNAs in relevant mouse models of AD and PD with the hope that this BlisRNAs will reduce pathology in a sustainable manner, without toxicity. “Since we developed each BlisRNA to be able to target all mRNA isoforms of human, mouse and primate ortholog genes, we can quickly test the same BlisRNAs in primates and ultimately in human clinical trials, if our studies in mice are successful,” explained Dr. Mourelatos.

Principal Investigators: Michael Haney, PhD, Saar Gill, MD, PhD, and Frederick “Chris” Bennett, MD

“Variants in the gene APOE have been shown to dramatically decrease the risk of developing Alzheimer’s disease (AD), however there are severe lipid related side effects outside the brain due to APOE expression in the peripheral immune system,” said Michael Haney, PhD, Assistant Professor of Pathology and Laboratory Medicine and principal investigator of this study. “The goal of this project is to develop engineered myeloid cell therapies that introduce AD-protective APOE variants into brain resident immune cells while sparing the peripheral immune system.”

Dr. Haney and his fellow investigators are examining whether replacing microglia with protective APOE variants is sufficient to inhibit progression of AD pathology in mouse models of AD -- and if so, which APOE variants are most effective in this.

Their work combines recently developed microglia replacement approaches with large scale CRISPR based gene editing of stem cells which enables them to quickly test the effect of many different variants of the APOE gene in AD progression. “This combination of this cell therapy approach with gene editing of the APOE gene is the first of its kind,” said Dr. Haney.