Atara Biotherapeutics Study Links Epstein-Barr Virus Infection with MS

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Analysis of post-mortem brain samples from multiple sclerosis (MS) patients and healthy individuals (without neurologic disease) showed that while signs of Epstein-Barr virus (EBV) infection are present in both groups of brains, EBV-positive immune cells were more prevalent and densely populated in the MS brain.

The study reporting those findings, ā€œMolecular signature of Epstein-Barr virus infection in MS brain lesions,ā€ was published in the journal Neurology: Neuroimmunology & Neuroinflammation, the official journal of theĀ American Academy of Neurology.

EBV infection is estimated to affect about 95% of adults worldwide, and previous studies have suggested a potential causal link between EBV infection and the risk for MS. These studies reported that MS patients had higher levels of antibodies against EBV than non-MS individuals, but follow-up studies have failed to find the same results.

Now, researchers analyzed autopsied brain samples from a MS brain tissue bank and from healthy, non-MS samples (controls).

They detected signs for the presence of EBV in 93% of MSĀ brain samples, but also in the controls, although to a less extent (78%).

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EBV infects immune B-cells, and the results showed that 85% of MS brain samples contained a higher percentage of B-cells positive for EBV-encoded RNA. In contrast, almost none of these cells were found in brain samples from controls.

ā€œTheĀ NeurologyĀ publication extends the growing body of evidence linking EBV infection and MS using a well-characterized MS brain tissue bank,ā€ Chris Haqq, MD, PhD, said in a press release. Haqq isĀ executive vice president of research and development and chief scientific officer ofĀ Atara Biotherapeutics.

ā€œWe observed that EBV is present in both MS and control brains, with EBV-infected B-cells and plasma cells more prevalent and localized to MS brain lesions,ā€ Haqq said.

Within immune B-cells, EBV switches between latent and lytic forms. The latent form is a way for the virus to evade the host’s immune system, whereas the lytic form corresponds to a state in which the virus replicates more actively. EBV infection was detectable in both MS and non-MS brains. although latent virus was more prevalent in MS brains, and lytic virus was restricted to chronic MS lesions.

ā€œTaken together, our results that are derived from a well-characterized MS brain tissue bank support previous studies demonstrating the presence of EBV in the MS brain,ā€ the team concluded.

ā€œThese findings advance the understanding of EBVā€™s potential role in MS pathogenesis and provide support for targeting EBV-infected immune cells associated with chronic MS lesions as a potential treatment for this severe autoimmune disorder,ā€ Haqq said.

Atara is developing two therapies, ATA188 and ATA190, to eliminate EBV-infected Ā B-cells in the central nervous system that can induce autoimmune responses and potentially contribute to MS development. Early results suggest these therapies can induce clinical improvements in MS symptoms.