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Ideally, we want to deliver MS drug therapies directly to the site of inflammation, the brain. This is likely to mean that they have their greatest effect and keep side effects to a minimum. Unfortunately, the body has many processes in place to stop this happening easily and developing ways to deliver drugs straight into the brain is challenging.
Mitoxantrone (MTX) (Novantrone) is a drug that has been registered to treat MS in Australia (and overseas) for many years and is known to be effective in preventing relapses. The use of MTX however, has been limited by significant side effects, such as heart toxicity and leukaemia, which become riskier with each subsequent dose, thereby preventing widespread use in many people living with MS.
In the laboratory, Associate Professor Bruestle and her team have developed a way to package the MTX drug into a fat-based particle called a liposome (LMTX), which may act as a shuttle to take the drug inside the brain. By doing this, the MTX can be delivered to the site of inflammation. Additionally, the serious side effects may be minimised using this technique as the MTX is kept away from healthy tissue and lower levels of the MTX are needed to achieve the same effect.
This type of study is known as a “proof of concept” study (POC), and if successful, the hope is that the technique could be explored in other drug treatments for MS, enabling them to also enter the brain to have their greatest effect and to minimise side effects.
In the first part of her project, Associate Professor Bruestle investigated the safety and effectiveness of LMTX in a relapsing remitting model of MS. As a starting point, a single dose of LMTX was given, which had no impact on symptom severity or relapse frequency. Ongoing work is seeking to determine an LMTX dose that reduces symptoms and relapse frequency
Associate Professor Bruestle and her team next studied the interactions between liposomes and immune cells to understand the mechanism underlying LMTX. They found that liposomes preferentially interact with a specific immune cell population in circulating blood and the spleen in laboratory models of MS and under normal circumstances. These cells are reduced during LMTX treatment. Another population of these cells were detected in the brain and spinal cord in laboratory models of MS, which increased with disease severity. Liposomes have also been found to strongly interact with B1 cells, a type of immune cell, in the spleen.
Associate Professor Anne Bruestle and her team have confirmed that liposomes are able to enter the brain and spinal cord and that delivery to here is dependent on the presence of inflammation. This suggests that liposomes are appropriate vehicles for the delivery of therapies to the brain and spinal cord during inflammation.
This work has been presented and several national conferences.
Updated: 31 March 2022
Updated: 19 January, 2021
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.
$235,000
3 years
