All treatments for MS come with benefits as well as potential side effects. Many treatments dampen the immune response to reduce brain inflammation, but one of the downsides is that this also increases the risk of infection.
Another issue with MS treatment is that it is difficult to tell that a medication is not working until the person has a relapse.
Everyone responds to MS medications differently, so an important research goal is to devise a method for early detection of response to treatments: both suppression of MS activity, and infection.
In this project Professor David Tscharke and his team studied response to the disease modifying therapy, cladribine. Cladribine temporarily depletes a range of blood cells thought to be part of the attack on the nervous system in MS, with the idea that when they come back, the immune system is “reset”, giving longer protection.
This project compared a group of people with MS who were being treated with cladribine over three years with a matched group of people without MS. Blood samples were analysed using two advanced methods. The first looked for evidence of any unusual infections and the second looked for whether cladribine was having any discernible effect either on MS or the immune system.
No one treated with cladribine showed any evidence of infection. On the contrary, Epstein-Barr virus (EBV), a virus that has been associated with MS, might be reduced briefly after treatment.
A marker of disease activity in MS, called “neurofilament light”, decreased within the first six months of treatment. Neurofilament light indicates nerve damage, so this reduction suggests cladribine is successfully suppressing active disease. However, this was not consistent enough to be a useful marker of treatment effectiveness.
The team found a hormone that was associated with the regrowth of blood cells at higher levels after cladribine treatment. This might help us understand how the body replaces blood cells after depletion.
Finally, five proteins were found at higher levels in the blood of people with MS, irrespective of treatment. The team is continuing to investigate whether these might tell us something about the origin of MS.
Overall, this study supports the safety of cladribine in terms of the effects of immunosuppression on susceptibility to infections.
It could provide further peace of mind for people with MS who are treated with cladribine, because there was no evidence of increased infection, even using the highly sensitive detection methods in this study.
This work provided new findings that could help in our understanding of the role of EBV infection and specific human proteins in MS, and how the immune system is reconstituted after depletion.
This was presented at a national conference in 2025, with a publication in preparation.
Updated: 31 March 2025
$25,000
2020
1 year
Current project
