Herpesvirus therapies

The rationale

Battle Biotech’s work builds on the hypothesis that common, lifelong herpesviruses — carried silently by most adults — are a major driver of Alzheimer’s disease and other neurodegeneration types. Furthermore, the type and severity of neurodegeneration may depend upon the combination of herpesvirus types, strain variants, and viral load, in combination with the person's genetic susceptibility. Brain inflammation from stroke or traumatic brain injury can release chemokines that attract infected immune cells. For example, Epstein-Bar virus infected B cells upregulate their cell-surface chemokine receptors, and can traffick to the site of brain injury where inflammatory cytokines cause the Epstein-Bar virus to reactivate, thereby infecting nearby endothelial cells, astrocytes, and oligodendocytes, and their progenitors. Rather than one pathogen acting alone, several human herpesviruses can converge at a site of inflammation. For example, a bilateral cluster of neurons located in the brainstem called the locus coeruleus shows abnormal tau accumulation and pretangles in children and young adults, and is decimated decades later in Alzheimer's diseased brain. Locus coeruleus degeneration also occurs in Parkinson's disease, Dementia with Lewy Bodies, and Frontotemporal Lobar Degeneration. Alphaherpesviruses (HSV-1, HSV-2, and VZV) are the only human herpesviruses known to infect neurons by traveling retrograde through axons to reach the cell nucleus. Alphaherpesvirus infected locus coeruleus neurons can then attract immune cells infected with other herpesvirus types, the combination thereof could determine disease, age of onset, and rate of progression. A manuscript describing the sequential steps of how herpes simplex virus-1 can reach the locus coeruleus and cause regional-specific degeneration is currently in preparation. Understanding this process is our best chance of developing strategies to stop progression of herpesvirus-mediated neurodegeneration.

Because significant damage is caused by secreted factors and viral exosomes, a small number of infected cells can injure many neighbouring cells. The therapeutic goal is to interrupt that cycle at its source — upstream of irreversible neurite collapse and Wallerian degeneration. One way to disrupt the release of secreted factors is to target the viral protein in each herpesvirus type that hijacks the host multivesicular bodies causing the release of viral exosomes containing viral proteins. The human cytomegalovirus and Epstein-Bar virus tegument viral proteins pp150 and gp350, respectively, interact with host proteins allowing them to hijack the multivesicular bodies for generation of viral exosomes. This process and therapeutic RNAi compositions and treatment is disclosed in pending US patent application no. 19/584,979 filed May 5, 2026, priority date 11/5/2023.

How the approach works

In an infected cell, multivesicular bodies are hijacked to package viral exosomes that are released in bulk into the extracellular space and taken up by neighbouring cells. Battle Biotech’s RNA-interference antiviral strategies are designed to prevent viral reactivation and the release of these secreted factors. Note that individuals taking an antiviral nucleoside or nucleotide analog, such as acyclovir, will not prevent the secretion of viral proteins or exosomes. This is because the virus uses the host RNA polymerase to transcribe viral mRNA. However, reducing virus genome replication, and thus spread, can decrease viral load and thereby limit the secretion of viral proteins and exosomes. Herpesviruses increase reactivation with increasing age. A high level of blood antibodies targeting particular herpesvirus proteins may indicate increased viral reactivation.

Intellectual property

Sole inventor: Dr. Richelle Cutler. Programmes are research-stage and investigational; nothing here describes an approved therapy or constitutes medical advice.

The science behind it

The full argument, its figures, and its evidence are set out in the Oskar Fischer Prize entry and its references, with an independent evaluation in the scientific analysis.