Press Release: Indiana University School of Medicine chooses MOLECUBES to accelerate their research supporting the MODEL-AD and TREAD-AD Open Science Grants.

Press Release: Indiana University School of Medicine chooses MOLECUBES to accelerate their research supporting the MODEL-AD and TREAD-AD Open Science Grants.

Abstract Version:

MOLECUBES NV, in partnership with LabLogic Systems Inc., has recently installed a β-X-CUBE imaging platform in the lab of Prof. Paul R. Territo at the Indiana University School of Medicine for their research supporting the MODEL-AD and TREAT-AD grants provided by NIH/NIA as consortium open science grants. The goal of these grants is to evaluate and characterize new animal models for Late Onset Alzheimer’s Disease (LOAD) and use these newly acquired insights to evaluate target engagement of novel and existing pharmaceuticals. As such, this work will advance the understanding of LOAD and provide the scientific community with an extended toolbox to accelerate research in this therapeutic area. MOLECUBES is proud to support this initiative with their high-end high throughput imaging platform that will generate statistically relevant data for cross-sectional and longitudinal deep-phenotyping of new LOAD models. Moreover, upon full characterization, the new PET/CT will be utilized to provide translationally relevant pharmacodynamic readouts of novel pharmaceutical target engagement in the MODEL-AD and TREAT-AD Preclinical Testing Core’s validated drug testing pipeline. Importantly, this approach will employ the same tools, techniques, and scientific rigor employed in clinical drug trials to advance our understanding of disease progression and accelerate the development of the next generation pharmaceuticals for LOAD.

Long Version:

The Indiana University School of Medicine has recently acquired the latest generation preclinical PET/CT imaging platform from MOLECUBES NV. The B- and X-CUBE scanners will be installed and managed by Paul R. Territo, Ph.D. These instruments will be used in meeting the goals outlined in the major grants that supported the purchase of the instrument as described below.

NIH/NIA Consortium Open Science Grants:

MODEL-AD – Model Organism Development and Evaluation for Late Onset Alzheimer’s Disease

$25M – 5 Year Grant to Indiana University School of Medicine, The Jackson Laboratory (JAX) and Pittsburg University

Bruce T. Lamb, Ph.D., Director and Co-PI.  IU School of Medicine

Paul R. Territo, Ph.D., Co-PI, IU School of Medicine. Preclinical Testing Core Leader

Gareth Howell, Ph.D., Co-PI, The Jackson Lab.  Disease Modeling Project Core Leader

Greg W. Carter, Ph.D., Co-PI, The Jackson Lab. Bioinformatics and Data Management Core Leader

The MODEL-AD consortium has been established by the National Institute on Aging to: 1) Develop the next generation of in vivo Late Onset Alzheimer’s’ Disease (LOAD) models based on mining human bioinformatics data; 2) Instituting standardized and rigorous process for characterization of animal models which align the pathophysiological features of AD models with corresponding stages of clinical disease using translatable biomarkers via the Disease Modeling Project (DMP) core; 3) Establish guidelines for conducting rigorous pharmaceutical testing in animal models via the Preclinical Testing Core (PTC); and 4) Ensure rapid availability of animal models, protocols and validation data to all researchers for development.

In the MODEL-AD DMP, the instrument will provide both cross-sectional and longitudinal deep phenotyping of new mouse models of LOAD using tracers that evaluate perfusion (64Cu-PTSM), metabolism (18F-FDG), beta amyloid (18F-AV45) and Tau (18F-AV1451). This deep phenotyping provides an opportunity to evaluate how the risk alleles in these LOAD models develop pathophysiological changes using the same technology and radiopharmaceuticals that are being employed in the clinical setting.

Once the models have been fully characterized, the MODEL-AD PTC will utilize the new PET/CT to evaluate target engagement of novel pharmaceuticals in the PTC’s validated drug testing pipeline. This approach provides translational pharmacodynamic readouts of drug efficacy in LOAD mouse models matched to novel pharmaceuticals which have a well-established mechanism of action, and employ the same tools, techniques, and scientific rigor employed in clinical drug trials.

TREAT-AD – TaRget Enablement to Advance Therapy Development for Alzheimer’s Disease

$36M – 5 Year Grant to Indiana University School of Medicine, Purdue University

Alan D. Palkowitz, Ph.D., Director and Co-PI. IU School of Medicine

Bruce T. Lamb, Ph.D., Co-PI.  IU School of Medicine

Kun Huang, Ph.D.  IU School of Medicine. Bioinformatics and Comp. Biology Core Leader

Timothy Richardson, Ph.D., IU School of Medicine.  Medicinal Chemistry Core Leader

Andrew Mesecar, Ph.D., Purdue. Structural Biology and Biophysics Core Leader

Zhong-Yin, Zhang, Ph.D., Purdue.  Assay Development and HTS Core Leader

 

The TREAT-AD consortia is charged with designing, developing and testing the next generation of novel pharmaceuticals for LOAD. This multi-disciplinary team comprises scientists at IU School of Medicine and Purdue University and will use informatics to select key targets known to drive disease progression, and then design and produce a series of compounds suitable for pharmaceutical testing. As part of this process, PTC, headed by Paul R. Territo, will evaluate these novel pharmaceuticals by employing translationally relevant pharmacodynamic readouts of drug efficacy via PET/CT imaging of established radiopharmaceuticals. In this context, the use of PET/CT will provide pharmacodynamic readouts of drug efficacy in LOAD mouse models and will dramatically accelerate the development of these novel pharmaceuticals by employing standardized workflows, techniques and scientific rigor utilized in clinical drug trials.

 

Why Molecubes:

To achieve the goals outlined in the MODEL-AD and TREAT-AD grants, the Territo lab will be scanning between 800-1400 mice per year. The team at IU was looking for a system, which has high sensitivity, resolution, and uniformity along with well-established and easy to follow workflows that would facilitate rapid multi-animal acquisition and reconstructions. Moreover, the Molecubes PET/CT system has been rigorously tested according to NEMA standards, whose approaches are used to qualify clinical instrumentation for clinical operations, helps to ensure the translational relevance of these studies. Since both MODEL-AD and TREAT-AD are part of NIH/NIA’s Open Science program, a key criterion in the selection of a system was the ability to disseminate acquisition and reconstruction protocols and techniques rapidly, thus ensuring reproducibility needed for deep-phenotyping and pharmaceutical testing in AD.

In the context of the MODEL-AD, the DMP is focused on the production of the next generation mouse models of Late Onset Alzheimer’s Disease (LOAD) and will be deep phenotyped via PET/CT. These model systems will be combined with novel pharmaceuticals generated by the TREAT-AD consortia (or the AD community) and submitted to the PTC for drug testing using translationally relevant radiopharmaceuticals and workflows on the Molecubes PET/CT imaging platform.