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Natalizumab (Tysabri) is a medication currently available to people with relapsing remitting MS. While this treatment can be very effective in reducing the impact of MS, as with all medications it can also have side effects. One rare but devastating risk of natalizumab treatment is the development of progressive multifocal leukoencephalopathy (PML), a viral infection that attacks the brain.
Currently, there is no accurate way to determine how effective natalizumab is in each individual, and as such all people with MS receive the same dose and have the same monthly dosage schedule. In some cases, this may be higher than needed, and unnecessarily increase the risk of PML in these people. This project aims to address this issue by testing the effectiveness of natalizumab in people being treated for MS. This team will use a newly developed test, called a leukocyte adhesive function assay, at various time points after the natalizumab infusion and compare the results to other traditional methods. It is hoped that the new method will provide more accurate information that will allow natalizumab dosing to be tailored for individuals and if possible, lower the dose and reduce the risk of PML.
Natalizumab works by blocking an “adhesion molecule” on immune cells. This adhesion molecule normally allows activated immune cells to attach to the walls of blood vessels in the brain, from which they can invade through the vessel wall into the brain tissue. The aim of the new blood test is to measure how effectively natalizumab is blocking this adhesive capacity of the immune cells.
The first aim of the project is to define the “normal ranges” of the new blood test: that is, to see how adhesive immune cells are in the absence of the drug. Thus far, the test has been conducted in 20 people with untreated MS, and in 40 people without MS. Using this data, Dr Blum’s team has defined preliminary normal ranges. They have also found that the test results differ in people with untreated MS compared to people without MS, that is, that the adhesive properties of the immune cells are altered in MS.
The second aim is to measure how long a natalizumab infusion remains effective in the body. To do this, the team is measuring adhesive properties of the immune cells at various timepoints after infusion. To date, 18 blood samples have been tested in this arm of the study. Interestingly, they have shown that natalizumab remains maximally effective not only at 4 weeks after infusion (when people would normally be re-dosed) but also at 6 weeks after infusion. When measured 8 weeks after infusion, there were big individual differences between several people with MS, with one participant still retaining maximal drug effect, while another retained only a very low effect.
The outcome of this study has the potential to change the current treatment schedules for natalizumab therapy, reducing side effects and maximising the benefits of this potentially highly effective medication for people with MS.
A manuscript to be published in a scientific journal is currently in preparation for this work.
Updated: 31 March 2022
Updated: 05 January, 2019
Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.
Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.
Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.
$75,000
3 years
