<scp><i>In Vivo</i></scp>Assays – Discovery and Development of New Antifilarial Drugs in Companion Animals

Sager, Heinz; Lizundia, Regina; White, William H.

doi:10.1002/9783527823413.ch17

Cited by 1 publication

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“…The use of normally non-permissive rodent models for drug assays with clinically important filariae can be expected to improve the efficiency and productivity of antifilarial discovery and development operations. Current paradigms typically employ a model parasite system to prioritize compounds active in preliminary phenotypic or mechanism-based screens; see [ 44 – 48 ]. The major filarial species targeted for chemotherapy, O. volvulus and Wuchereria bancrofti for humans and D. immitis for companion animals, have highly restricted host specificity and so mandate that only the most promising lead compounds can be evaluated in limited human clinical trials.…”

Section: Improved Drug Screening: Small Animal Modelsmentioning

confidence: 99%

New paradigms in research on Dirofilaria immitis

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2023

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Background Since the advent of ivermectin (along with melarsomine and doxycycline), heartworm has come to be viewed as a solved problem in veterinary medicine, diminishing investment into non-clinical research on Dirofilaria immitis. However, heartworm infections continue to pose problems for practitioners and their patients and seem to be increasing in frequency and geographic distribution. Resistance to preventative therapies (macrocyclic lactones) complicates the picture. The use of chemotherapy for other kinds of pathogens has benefitted enormously from research into the basic biology of the pathogen and on the host-pathogen interface. A lack of basic information on heartworms as parasites and how they interact with permissive and non-permissive hosts greatly limits the ability to discover new ways to prevent and treat heartworm disease. Recent advances in technical platforms will help overcome the intrinsic barriers that hamper research on D. immitis, most notably, the need for experimentally infected dogs to maintain the life cycle and provide material for experiments. Impressive achievements in the development of laboratory animal models for D. immitis will enhance efforts to discover new drugs for prevention or treatment, to characterize new diagnostic biomarkers and to identify key parasite-derived molecules that are essential for survival in permissive hosts, providing a rational basis for vaccine discovery. A ‘genomics toolbox’ for D. immitis could enable unprecedented insight into the negotiations between host and parasite that enable survival in a permissive host. The more we know about the pathogen and how it manipulates its host, the better able we will be to protect companion animals far into the future. Graphical Abstract

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Section: Improved Drug Screening: Small Animal Modelsmentioning

confidence: 99%

New paradigms in research on Dirofilaria immitis

Geary

2023

Parasites Vectors

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In VivoAssays – Discovery and Development of New Antifilarial Drugs in Companion Animals

Cited by 1 publication

References 32 publications

New paradigms in research on Dirofilaria immitis

New paradigms in research on Dirofilaria immitis

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