2017-2018 CJD Foundation Research Grant Recipients

Dr. Hermann Clemens Altmeppen
Institute of Neuropathology
University Medical Center – Eppendorf, Hamburg, Germany

“Investigating the Potential of the Neuroprotective N1 Fragment of the Prion Protein as a New Treatment Against Prion Diseases”
A relevant fraction of the cellular prion protein (PrPC) on our neurons is constantly cut into smaller pieces by molecular scissors termed “proteases”. These cleavages reduce amounts of the prion protein as a substrate for the detrimental three-dimensional misfolding underlying fatal prion diseases. In addition, cleaved parts of the prion protein are released from the neuronal surface as soluble fragments. The latter may act as protective factors by binding to and neutralizing the pathological form of the prion protein (PrPSc), thus interfering with prion disease progression and toxicity. Our research aims to employ the evolutionary conserved cleavages of the prion protein for therapeutic purposes to fight devastating neurodegenerative conditions such as Creutzfeldt-Jakob Disease.

Leonardo Cortez, Ph.D.
Centre for Prions and Protein Folding Diseases,
University of Alberta, Edmonton, Alberta, Canada

“Isolation and Strain-Specific Characterization of Pathogenic CJD Prion Particles”
One of the hallmarks of prion diseases is the accumulation of aggregated forms of the prion protein that range in size from few nanometers to particles greater than hundred micrometers. Very little is known about which of these particles are the most pathogenic. Treatments that focus on removing or blocking prion particles are hindered without this information. In this project, we will isolate prion particles from genetic and spontaneous CJD human brain samples using Asymmetric Flow Field-Flow Fractionation (AF4). AF4 is a flow-based separation method with higher resolution range than classical fractionation techniques and particularly useful in the study of protein aggregation diseases. We will use a wide variety of biochemical and biophysical techniques to characterize the isolated human prion particles and determine which of them are the most pathogenic and potential targets for therapeutic intervention in human prion diseases.

David A. Harris, M.D., Ph.D.
Department of Biochemistry, Boston University School of Medicine

“Highly Synergistic Combination Therapy for Prion Diseases”
This project will test a potentially powerful combination therapy for prion disorders that aims to block two distinct steps in the disease process: (1) the accumulation of infectious prions; and (2) the ensuing nerve cell damage caused by activating specific cellular pathways. We predict that combining drugs that target both of these steps will be significantly more effective than current mono-therapies, which are designed exclusively to reduce prion accumulation.

Allison Kraus, Ph.D.
Rocky Mountain Laboratories, Montana

“Investigation of Prion Inactivation by Reactive Oxygen Species in Vivo”
Hypochlorous acid (HOCl) is a reactive oxygen species (ROS) produced naturally by the immune system as a defense response to invading pathogens. Recently, we have shown that hypochlorous acid solutions are potent inactivators of prions and I have evidence that human immune cells can inactivate prions through production of HOCl and related compounds. The objectives of my research include investigating how HOCl and ROS species produced in a host can influence prion inactivation and removal following prion infection.

Sylvain Lehmann, Ph.D.
Institute for Regenerative Medicine and Biotherapy, University of Montpellier, France

“Innovative Human 3D Neural Network Model for the Efficient Propagation of Human Prions”
In this project, Dr. Lehmann will build a 3D human cell culture model that will emulate, “in a dish,” the very complex structure of the human brain. Using such a model will greatly increase the relevance of mechanistic and therapeutic studies to humans. This model will allow him to study prion propagation and subsequently develop high throughput drug screening experiments.

Rodrigo Morales, Ph.D.
Mitchell Center for Alzheimer’s Disease and Related Brain Disorders
Department of Neurology, University of Texas-Houston Medical School

“Systematic Evaluation of the Zoonotic Potential of Different CWD Isolates”
The objective of this proposal is to assess, in a detailed and systematic manner, the direct and indirect (by co-existing animal species) zoonotic potential of different Chronic Wasting Disease (CWD) isolates.

For more information on past recipients of the CJD Foundation Research Grants, visit https://cjdfoundation.org/grant-recipients