Preventing and Treating Filarial Disease - (HJF 470-17)

Filarial worms are thread-like parasites that cause severe damage to the lymphatic system as manifested by painful and abnormal swelling of body parts. Current strategies to stop infection includes annual Mass Drug Administration (MDA) to the entire at-risk population (human and animal) for 6-10 years. However, the drugs used currently have limited effect on infective adult parasites .

Researchers at the Uniformed Services University for the Health Sciences (USU) and their partners at the National Institute for Allergies and Infectious Diseases (NIAID) have developed new therapeutics that include small molecules and antibodies that kill adult filarial worms (macrofilaricidal) for effective infection prevention.

Applications and Advantages

Macrofilaricidal: Improved therapeutic agents that kill adult parasitic worms
PAN helminth activity: Inhibit activity of proteins essential for survival of adult worms; can be effective against broader spectrum parasitic helminths
Antibodies/Vaccines: Possible alternatives to expensive and logistically burdensome mass drug administrations to animals and humans
Synergistic: Demonstrates strong synergistic toxicity towards adult worms when used in combination existing anthelmintic drugs

Innovation Description

Filariasis is a neglected tropical disease caused by thread-like worms (helminths) that live in human lymph systems. Mature females release infective larvae into circulating blood which are then ingested by feeding mosquitoes. Larvae spread to new hosts (human or animal) through mosquito bites. Adult worms cause chronic disability due to limb and scrotal swelling.

Commonly used anthelminthics are potent against the larvae (microfilariae) but do not eliminate adult worms that can live up to 5-10 years and cause several adverse effects in patients infected with the filarial eyeworm Loa loa. At present, annual MDA and mosquito control is the only strategy used against infection worldwide. There is a critical need to develop drugs that can eliminate adult worms and vaccines to control and eradicate the infection.

Our researchers have identified chemical compounds and antibodies that inhibit proteins essential for survival of adult parasitic helminths including filarial worms (Fig. 1). The proteins Uridine 5’-Diphospho-Glucuronosyltransferase (UGT) and immunoglobin I-set domain containing protein (IgI-DCP, Bma-LAD-2) and their homologs are shared across filarial and non-filarial helminths. Hence, inhibitors and antibodies developed against Igl-DCP and/or UGT may also be effective against a wide range of helminth species.