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AC-8

Herpes Simplex Virus - Mediated Ocular Disease HSV is the most common viral infection in humans and is a significant cause of infectious eye disease. HSV-related ocular infections occur primarily as recurrent herpetic conjunctivitis, keratitis, and iritis, and are a significant health problem affecting up to 10 million individuals worldwide. Complications due to repetitive reactivation of ocular HSV leads to cumulative damage to the eye and is the most common cause of corneal blindness in the United States and infectious blindness in the Western world.

Current Treatment Generally, patients are treated with ocular eye drops or ointments (topical trifluridine 1% solution 9 times daily or vidarabine 3% ointment 5 times daily). Corneal toxicity is a frequent adverse effect of chronic use of these topical antiviral agents. Oral acyclovir and pro-drug is also used. Attempts at using acyclovir for the reduction of recurrences leading to HSV mediated blindness have been less than satisfying.

  • AC-8 :: Images
  • AC-8 :: Images
  • AC-8 :: Images

Calmuneʼs anti-HSV Antibody, AC-8 Antibodies have been shown to interfere with virus axonal spread and to restrict virus expression in sensory neurons. In fact, administration of HSV-specific antibodies (derived from species other than Homo sapiens) reduces the number of acutely infected ganglionic neurons following viral challenge and prevents spread of virus to the CNS. Antibody-mediated restriction of virus expression in vivo is also suggested by the demonstration that antibodies can be protective in animal models even if administered 24-48 hours after HSV-infection when the virus is already in the peripheral nervous system and has already reached the ganglia. Antibodies can both reduce viral load and prevent interneuronal viral spread – both mechanisms involved in the development of ocular keratitis in individuals infected with herpes virus. Passive immunization with monoclonal antibodies has proven effective in animal models of herpetic keratitis, and it is likely that human recombinant antibodies could represent a valid prophylactic tool, especially in recurrent cases. Given the serious complications of viral spread from the trigeminal ganglion into the eye – an antibody that restricts transport of the virus could prevent ocular complications in infected individuals. AC-8 is a potent fully human Fab monoclonal antibody that is reactive against both HSV-1 and HSV-2 and prevents cell-to-cell virus spread, including neuronal spread to epithelial cells, in a model of herpes infection. Furthermore, AC-8 can reduce virus expression in explanted trigeminal ganglia infected with herpes virus and when administered to infected animals was found to strongly localize with HSV-infected nerve fibers and interfere with HSV axonal transport - a key aspect of the underlying pathobiology of ocular keratitis in herpes virus infections.

AC-8 has completed its discovery phase, and is now undergoing preclinical testing to evaluate the therapeutic potential of topically administered AC-8 in preventing the onset of ocular keratitis following HSV infection.
 
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