Ixazomib is being tested as a potential treatment for relapsing and progressive multiple sclerosis (MS).
Ixazomib for relapsing and progressive MS: Phase I
- Ixazomib causes the death of faulty plasma cells in brain tissue which have been linked to MS progression.
- Ixazomib has not been tested in people with MS but has been used to treat myeloma, a cancer of the bone marrow.
- The most common side-effects of include: chest infections, gastrointestinal discomfort, oedema (fluid retention), skin rash and back pain.
Ixazomib targets plasma cells, a type of immune cell which develops from B cells. Plasma cells produce the antibodies which appear as oligoclonal bands (OCBs) in cerebrospinal fluid. Recent research suggests that plasma cells can live in brain and spinal cord tissues for a long time and may be responsible for long term progression, sometimes referred to as smouldering MS.
Ixazomib belongs to a group of drugs known as proteasome inhibitors. Proteasomes are structures present in all cells in the body. They clear up unwanted old proteins so that they don't disrupt the normal functioning and growth of the cell. Faulty plasma cells make lots of proteins and are reliant on proteasomes to continue to grow and function. Ixazomib binds to proteasomes and prevents them breaking down unwanted proteins, causing the faulty plasma cell to die.
Ixazomib is currently used as a treatment for myeloma, a type of bone marrow cancer.
Ixazomib is taken as a capsule on days 1, 8 and 15 of a 28 day treatment cycle.
Ixazomib has not been tested in people with MS, so approval for the SIZOMUS study required an initial safety analysis. The first five participants completed 3 months (three participants on ixazomib, two on placebo) and showed no significant side effects. The study has now been approved to start full recruitment.
SIZOMUS - ixazomib compared to placebo
This phase I/II study will recruit 72 participants with relapsing remitting and progressive MS. Participants with relapsing remitting MS must be stable on a disease modifying drug which they will continue to take. Participants will take either ixazomib or placebo for two years. There are two main aims of this study: firstly, to test whether ixazomib is safe and well-tolerated by people with MS; and secondly, whether it can reduce or eliminate oligoclonal bands from cerebrospinal fluid (CSF). Side effects will be recorded and oligoclonal bands in CSF (involving lumbar punctures) measured at the beginning of the study and at 24 months.
Estimated completion date August 2023
Further details of the study
More details of the study can be found on the MS Research blog.
The most common side-effects of ixazomib include:
- chest infections
- nausea
- vomiting
- constipation
- diarrhoea
- oedema (the retention of abnormally large amounts of fluid in the body, causing swelling)
- skin rash
- back pain.
Ixazomib can also cause low levels of platelets (a type of blood cell which helps the blood clot) and low levels of neutrophils (a type of blood cell involved in fighting infections).
