Uncovering the Hidden Potential: CAMs as a Game-Changer in HBV Treatment


Capsid assembly modulators (CAM) work by assembling flawed hepatitis B capsids and preventing the formation of new infectious viruses.

Capsid assembly modulators (CAM) work by assembling defective HPV capsids and preventing the formation of new infectious viruses.

Hepatitis B virus (HBV) is a chronic infection that affects millions of people worldwide. Despite advances in treatment, finding an effective cure remains a challenge. However, recent research has shown promising results with the use of a capsid assembly modulator (CAM). Could this innovative approach be the key to successful HBV treatment?

HBV is a major global health concern, with approximately 257 million people living with chronic HBV infection. Traditional therapies such as nucleos(t)ide analogs, reverse transcriptase inhibitors and interferon-alpha have limitations. They often need to be taken for long periods of time and can have troublesome side effects. Perhaps more importantly, these therapeutic modalities do not lead to a high cure rate as the virus can evade the innate immune system and establish chronic infections. Eluding scientists as well, this cunning viral ability has necessitated the search for alternative treatment strategies.

Earlier this month in a research article published in Hepatology, Dieudonné Buh Kum, Ph.D., of Aligos Therapeutics, and his colleagues explicated a potential breakthrough in the treatment of chronic hepatitis B with the class A capsid assembly modulator (CAM-A) compound RG7907 in a chronic hepatitis B mouse model. The study aimed to investigate the mechanism of action for RG7907 and its potential for achieving a functional cure for chronic hepatitis B.

CAMs work by encouraging the assembly of defective HBV capsids and preventing the formation of new infectious viruses. They can also induce disruption of preformed capsids, preventing new HBV infection.RG7907 was shown to induce apoptosis in HBV-infected cultured primary hepatocytes and hepatoma cells.The resulting extensive aggregation of the HBV core protein in the cell nucleus from CAM treated cells was hypothesized to have precipitated cellular death.

In an adeno-associated virus mouse model of HBV, CAM treatment resulted in a reduction of HBV antigens. A significant reduction in serum HBsAg and HBeAg was observed, along with the clearance of HBsAg, HBc, and HBV cccDNA from the liver, indicating potential efficacy in clearing the virus.

CAM treatment has also been found to restore suppressed innate immune responses against HBV, further enhancing its potential as a therapeutic approach. The researchers noted that gradually eliminating infected cells through CAM-induced apoptosis can lead to immune control or complete elimination of HBV infection. Cell death also promotes the regeneration of uninfected hepatocytes, contributing to the potential for a functional cure. It should be added that it is the process of mitotic regeneration of hepatocytes whereby the HBV episomal DNA is lost.

In an accompanying editorial, Adam Zlotnick, Ph.D., of Indiana University, emphasized the need for further research to understand the mechanisms by which CAMs induce apoptosis and the molecular triggers involved. They also mentioned the potential synergy between an apoptosis-inducing CAM and interferon therapy.

Zlotnick and his co-authors authors noted separate clinical trials of two CAMs, vebicorvir and bersacapavir. Although early achievement in nondetectable viral loads was observed, the therapeutic effect did not hold and HBV reemerged.

Many researchers see CAMs as having the potential to disrupt the assembly of viral core particles, ultimately inhibiting viral replication. This possibility has sparked hope for improved outcomes and a potential cure for chronic HBV infection.

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