Dr. Kathleen Frey, PhD

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Dr. Kathleen Frey, PhD
Professor of Pharmaceutical Sciences
College of Pharmacy and Health Sciences
Fairleigh Dickinson University

Project Title

Drug Design for Lymphatic Filariasis, a Neglected Tropical Disease

Project Details

Principal Investigator

Dr. Kathleen Frey, PhD
Professor of Pharmaceutical Sciences
College of Pharmacy and Health Sciences
Fairleigh Dickinson University

External Partner(s)

Nina Goodey, PhD
Professor of Chemistry and Biochemistry
Montclair State University

Project Period

July 1, 2026 to June 30, 2027

Project Description

Dr. Kathleen Frey has been awarded the FDU Seed Grant to support collaborative drug design research for lymphatic filariasis, a neglected tropical disease with very few safe and effective treatment options. Using a structure-based, computationally driven approach, Dr. Frey developed a focused screening library of antifolates for virtual screening to test against dihydrofolate reductase (DHFR) from Wuchereria bancrofti, the major parasitic worm that causes lymphatic filariasis in tropical countries. Several compounds have been identified computationally as potential inhibitors of Wb DHFR and will be experimentally tested by collaborator Nina Goodey’s lab. An additional goal of the project is to build structural selectivity into the identified compounds to reduce off-target binding to human DHFR. This strategy can reduce potential toxicity and major adverse drug reactions.

Problem Addressed

Lymphatic filariasis affects over 100 million people worldwide, and current treatment options such as ivermectin, albendazole, and diethylcarbamazine have limited efficacy and adverse drug reactions. Many of these drugs cannot kill the parasite at various lifecycle stages. This project aims to design and develop safe and effective inhibitors that will kill various lifecycle stages of Wuchereria bancrofti, the parasitic worm that causes the disease.

Who Will Benefit

This project can benefit individuals who have lymphatic filariasis and at-risk populations in tropical countries. Currently, it is estimated that there are 51 million people living with lymphatic filariasis worldwide. These people are in need of safer and more efficacious treatments. The research can also be extended to explore prevention methods for at-risk populations. In addition, this project can also support drug design and discovery research for our students and promote collaboration with other institutions.

Goals During the Grant Period

Using a collaborative multi-disciplinary approach, the goal of this project is to identify 3-4 compounds that can be further developed as a novel treatment for lymphatic filariasis. We have 2 specific aims to achieve this goal: 1) Characterize the binding affinities and structures of selected lead antifolates and helical peptide mimetics in complex with WbDHFR; and 2) Determine and optimize the selectivity of lead antifolate compounds. We will also submit grants to NIH (R15 AREA) and plan to continue writing proposals until the project is awarded.

Broader Impact

The development of safe and effective drugs for lymphatic filariasis is important as this disease is debilitating and affects the quality of life for over 100 million people worldwide. From a public health aspect, this research funds the preliminary research needed for drug design and discovery for a disease with unmet medical needs. Research from this project will also give students at FDU Health both computational and experimental research opportunities that will enhance their learning experience.