Novel Therapeutic Strategy for Human Cytomegalovirus (HCMV) Infection

Novelty: A novel therapeutic strategy for HCMV infection by modulation of the Wnt signaling pathway.
 
Value Proposition: HMCV infection is a serious threat for pregnant women and the immunocompromised, such as HIV/AIDS patients or solid organ transplant recipients. Currently, the main HCMV treatment is a six-week cycle of intravenous administration of ganciclovir (GCV), a viral DNA polymerase inhibitor. Given the long treatment cycle, side-effects, toxicity and GCV resistant viral strains, alternative treatments are highly desirable. This technology identifies a novel therapeutic approach for blocking HCMV replication by inhibiting the host-cell Wnt signaling pathway. Advantages include:

• Blocks HCMV replication at multiple stages of the viral replication process
• Inhibition of HCMV replication is independent of viral DNA-replication, so it could be used in parallel with current antivirals for a multi-drug therapy
• Works against GCV resistant HCMV

 
Technical Details: Johns Hopkins researchers have developed an effective way to inhibit HCMV replication using three ionophore-based antibiotics targeting the Wnt signaling pathway. Cell-based assays were carried out using human foreskin fibroblasts (HFF) to test the three antibiotics, which showed effective inhibition of HCMV with low toxicity. All three compounds could also inhibit GCV-resistant HCMV, suggesting a DNA replication independent inhibition, and a potential therapy for GCV-resistant HCMV. The compounds were able to prevent viral replication at multiple stages of the replication cycle. Further work examining the Wnt signaling protein levels demonstrated that both HCMV and ionophores independently disrupted Wnt signaling, suggesting HCMV replication requires tight regulation of the Wnt signaling.
 
Looking for Partners:  To develop & commercialize the technology as a therapeutic for HCMV infection.
 
Inventors: Ravit Boger
 
Patent Status: Granted US Patent 9,549,914
 
Stage of Development: Discovery
 
Data Availability: In Vitro
 
Publications/Associated Cases: Antimicrob Agents Chemother. 2013 Jun;57(6):2761-7

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