MS results from the immune system mistakenly attacking and destroying myelin, the protective layer that insulates nerves in the brain and spinal cord. Most current treatments available for MS act by suppressing or ‘resetting’ the immune system to stop this attack. Immunotherapy is a completely different approach to treating MS. Immunotherapy aims to ‘re-educate’ the cells of the immune system responsible for the MS attack to reduce the likelihood of a relapse.
Results of two clinical trials of an experimental new immunotherapy for people with MS have recently been published in the journal Neurology showing encouraging results.
Myelin is made up of a range of fat molecules and some proteins. In MS, the immune cells mistakenly target some of the protein components of the myelin, including parts of one protein known as myelin basic protein. The experimental immunotherapy, ATX-MS-1467, is made up of a cocktail of four different protein fragments from myelin basic protein. The protein fragments are injected under the skin and are able to ‘teach’ immune cells not to attack myelin basic protein.
This essentially re-trains the immune system to recognise myelin as ‘self’ with the hope of preventing the myelin damage seen in MS. Previous research had shown good results of ATX-MS-1467 in a laboratory model of MS. In the studies just published, the researchers conducted clinical trials in a small number of people with relapsing MS to test for safety (Phase 1b trial) and effectiveness (Phase 2a trial).
The Phase 1b clinical trial compared two routes of administration of the drug, intradermal injections (injections into the skin just below the outermost layer) and subcutaneous injections (deeper injections into the fat layer below the skin) and compared a range of doses in 43 people with relapsing MS. Participants were given an injection every two weeks for 16 weeks and then followed for a further 32 weeks. This study showed that while there were some mild and moderate side effects, ATX-MS-1467 was well tolerated and that the intradermal injections were a better way of delivering the immunotherapy.
Exploratory investigations of the effectiveness of the treatment in the Phase I study indicated that it may have some temporary effect in reducing the gadolinium enhancing lesions on magnetic resonance imaging (MRI), a marker of active disease but lesions returned to pre-treatment levels after the 32 weeks off the medication.
The Phase 2b clinical trial was then designed to more thoroughly examine the effectiveness of the treatment in 37 participants compared with baseline levels of disease. Participants were given treatment over 16 weeks and then followed-up for 16 weeks off treatment. As for the first trial, the Phase 2b trial showed that ATX-MS-1467 was able to reduce gadolinium enhancing lesions on MRI at the end of the treatment period but also showed that this reduction persisted over the shorter 16 weeks of follow-up. The Phase 2b trial also showed that ATX-MS-1467 reduced the number of new or enlarging lesions on MRI.
Participants did not have significant reductions in their expanded disability status scale (EDSS) or MS functional composite (MSFC) measurements, both of which assess levels of disability in the clinic, as a result of the treatment. However, the short duration of the trial would make it difficult to reliably detect any changes in disability.
These promising results imply re-training the immune system to prevent it’s attacks on myelin may be an effective strategy and further clinical trial testing of ATX-MS-1467 is warranted in larger groups of people with MS.