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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. These side effects therefore prevent the widespread use for many people living with MS.
In the laboratory, Associate Professor Anne Bruestle and her team have developed a way to package the MTX drug into a fat-based particle called a liposome, 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. 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.
Associate Professor Anne Bruestle and her team are making significant progress in their project on the use of liposome drug vehicles for treating MS. Initial experiments with liposomal mitoxantrone (LMTX) showed no immediate impact on MS symptoms or relapse frequency. However, ongoing research aims to determine the optimal dose of LMTX that effectively reduces symptoms and relapses.
The team focused on understanding how LMTX works by studying its interactions with immune cells. They discovered that liposomes selectively interact with specific immune cell populations in the bloodstream and spleen, both in MS models and normal conditions. These cells were reduced during LMTX treatment. Additionally, they observed an increase in liposome-interacting cells in the brain and spinal cord as MS severity worsened. Strong interactions between liposomes and B1 cells, a type of immune cell, were also found in the spleen.
Furthermore, the researchers confirmed that liposomes can enter the brain and spinal cord, but this delivery depends on inflammation. This indicates that liposomes can effectively transport therapies to these regions during inflammation.
The team is currently working on determining the lowest effective dose of LMTX in the MS model. They are exploring different strategies, such as reducing liposome quantity or drug concentration per liposome. Additionally, they are investigating the impact of LMTX on various immune cell populations in the blood and brain and spinal cord, as well as studying the interaction between liposomes and different subsets of immune cells. They have also developed protocols to isolate liposome-interacting cells from the brain and spinal cord, which will be vital for future experiments.
This research has the potential to revolutionise the treatment of MS by using liposome drug vehicles, leading to safer and more effective therapies.
Updated 31 March 2023
Associate Professor Bruestle and her team have made significant progress in their project on the use of liposome drug vehicles for treating MS. Their latest results show that this liposome-based version of mitoxantrone (LMTX) is over 10 times more effective in their laboratory models. This special “nano-packaging” also helps deliver the drug specifically to areas of the brain and spinal cord during inflammation, potentially making MS treatments both safer and more effective.
The team discovered that these liposomes are taken up by a newly-discovered type of immune cell, called eDCs, found in the central nervous system of a laboratory model of MS-like disease. This specific group of dendritic cells increases as MS symptoms worsen, suggesting that they’re strongly linked to the severity of the disease.
The team also found that the number and type of eDCs change as the disease progresses. By specifically targeting this unique group of cells with LMTX, they saw a significant reduction in inflammation and symptoms, suggesting that these cells could serve as both a marker for MS activity and as a new target for treatments. Importantly, this liposome technology allows the drug to reach the brain and spinal cord, especially during periods of neuroinflammation.
The team are now investigating whether a similar cell population is present in people with MS, which will hopefully lead to two important developments:
The team will continue to test these liposomal formulations, which not only boost the effectiveness of the drug by more than 10 times but also help deliver it to the central nervous system during periods where it is most needed. Their work could lead to better tools for tracking and treating MS in the future. The researchers are preparing a number of manuscripts for publication.
Updated 31 March 2024
$235,000
2021
3 years
Past project
