Australia Sets Aside $18M to Support MS Trials, EBV Research

The Australian government has announced that a record AU$18 million (about $13.5 million) from the Medical Research Future Fund will be used to support research into multiple sclerosis (MS) as part of its 2022–23 budget.

Grant opportunities will focus on increasing access to clinical trials and speeding the development of effective therapies for Epstein-Barr virus (EBV) infection, which is thought to be the leading cause of MS.

The funding will also be used to support studies aiming to shed light on how immune responses to viruses vary across individuals, and how this can be used to predict MS and identify new therapeutic approaches. Such information may be key to ultimately reducing the frequency and severity of MS and other diseases associated with viral infections.

“This is a welcome commitment with a focus on clinical trials and developing therapeutics for the Epstein Barr Virus,” Des Graham, chair of MS Australia and an associate professor at the Menzies Institute for Medical Research MS Flagship, said in the organization’s press release.

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EBV — mostly known for causing infectious mononucleosis, or mono — infects most people at some point in their lives, but its symptoms can be minor and often escape notice. After infection, the virus remains in the body in a dormant form inside B-cells — a type of immune cell implicated in MS.

While an increasing number of studies have suggested an association between EBV infection and MS, compelling evidence of a cause-and-effect relationship was lacking until early this year.

A study published in January, which followed more than 10 million U.S. military members, showed that infection with EBV, but not other common viruses, increased the risk of developing MS by more than 30 times, placing EBV as the leading cause of MS.

The data also demonstrated that levels of neurofilament light chain (NfL), a biomarker of nerve cell damage, increased after EBV infection in service members who later developed MS.

A subsequent, separate study provided a plausible explanation for the link between EBV infection and MS: structural similarities between an EBV protein and GlialCAM, a brain protein found at the surface of myelin-producing cells.

Myelin is the protective sheath around nerve fibers that is progressively lost in people with MS due to abnormal immune responses.

Due to these structural similarities, B-cells may accidentally recognize GlialCAM as foreign while trying to fight off EVB, mounting immune attacks against the brain protein as well.

While these findings strongly support EBV as a major risk factor for MS, infection alone is insufficient to cause the disease. A combination of genetic predisposition and/or other environmental factors may promote the development of MS.

Still, developing EBV vaccines or therapies against the virus could help to prevent MS and ease its severity.

Notably, MS Australia and MS Queensland supported the development of ATA190, Atara Biotherapeutics’ investigational EBV-targeting immune cell therapy that showed promise in a Phase 1 trial (ACTRN12615000422527) involving 10 people with progressive forms of MS.

Atara is now working on a similar therapy, called ATA188, that instead of using immune cells collected from patients, uses cells from healthy donors to be more scalable and efficient. The therapy is being tested in the EMBOLD Phase 2 trial (NCT03283826), which is enrolling up to 80 adults with progressive forms of MS and evidence of past or current EBV infection at sites in the U.S. and Australia.

MS Australia also noted that this latest funding plan follows an AU$4 million grant announced in December for a clinical trial testing nerve cell repair and protection therapies for MS, bringing the total support for MS research in the past four months to AU$22 million.

These grant allocations “have come at a critical pivot point; while the last 15 years have seen development of treatments that slow disease progression in people with relapsing remitting MS, we are yet to successfully repair and regenerate the damaged nerves in progressive forms of MS,” the organization stated in the release.