Corallopyronin A as antifilarial drug - A natural antibiotic product for the effective treatment of dirofilariasis

Ref.-Nr. 2838 - Veterinary

Keywords: heartworm (Wolbachia), dirofilariosis, dog, anthelmintic (anti-worm), anti-filarial, DZIF (Deutsches Zentrum für Infektionsforschung)

Canine dirofilariasis, commonly known as heartworm disease, is caused by the nematode parasites Dirofilaria immitis and D. repens and transmitted through mosquito bites into dogs. The parasites inhabits the heart and pulmonary arteries, causing damage to these organs. Wolbachia, the bacterial endosymbiont of the parasites, crucially regulate the nematodes’ life cycle. Standard treatment for dirofilariasis involves ivermectin prophylactically or melarsomine on the therapeutic level. However, these drugs are known to cause side effects and resistance.

Corallopyronin A (CorA) is a novel non-competitive inhibitor of the bacterial DNA-dependent RNA polymerase. CorA aims at slowly killing Wolbachia, thus avoiding strong inflammatory reactions. The IP package further comprises a production process of CorA, established on a 15,000 litre scale in preparation for GMP manufacturing, and a stable formulation for oral administration.

Vorteile

  • Effective treatment of canine dirofilariasis
  • Slow worm death prevents potential endotoxic shock
  • Oral administration of CorA
  • Stable formulation of CorA

Kommerzielle Anwendung

On behalf of the University of Bonn, PROvendis offers an access to rights for commercial use (patent applications, patents and know-how).

Aktueller Stand

Assessment CorA

Results

Production and formulation

  • USP, DSP
  • Chromatographic purification
  • Free flowing powder

 

Each up to 15,000 L

35 to 90 g batches

Gastro resistant capsules for oral application

Toxicology (non-GLP)

  • Off target profiling
  • Cyp inhibition
  • CYP 3A4 induction via PXR
  • MTD dog
  • 7-day repeated-dose dog

 

EC50 [µM]: A3= 11, PPARγ= 2.2, COX1= 8.2

No inhibiton of six recombinant human CYPs

EC50 [µM]: 12

1000 mg/kg; moderate, transient symptoms

0, 150, 450, 750 mg/kg bw/day

150 mg/kg bw/day: NOAEL (preliminary)

Cmax 208 µg/ml (d1) / 212 µg/ml (d7)

Safety Pharmacology

  • 14 day toxicity study in dogs
  • Cardiovascular effects in dogs
  • GLP toxicity

 

2024

Radiotelemetry, 2024 

Q4/2023 - Q2/2024

Technologie-Reifegrad

1 2 3 4 5 6 7 8 9
Versuchsaufbau in Einsatzumgebung

Relevante Veröffentlichungen

More information on IP status on request.

Becker T. et.al Eur J Pharm Biopharm (2023); Rox et al., Pharmaceutics. 2023; 15(1):131;

Ehrens et al., Front. Trop. Dis., Vol. 3 (2022); Krome et al., Nat Prod Rep 39:1705-1720;

Krome et al., Pharmaceutics 12 (2020):1105; Becker et al. Pharmaceutics (2022) 14:1657

An invention of the University of Bonn.

Dipl.-Biol. Kordula Kruber

kk@provendis.info
+49 208 9410530