Why is treating multiple sclerosis complicated and how this new treatment looks to solve these problems

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Multiple sclerosis (MS) is an autoimmune disease of the nervous system in which the immune system “mistakenly” produces antibodies to nerve cells that then destroy the myelin that surrounds the nerve fibers. The myelin sheath otherwise ensures good conduction of the electrical impulse through the nerve fiber, and due to damage to this sheath, people with MS have several symptoms. 

Attacks of the immune system on nerve cells can take place at intervals and then we talk about a relapsing form of MS, or a mild attack can be permanently present, and then we talk about progressive MS. A healthy lifestyle, the so-called anti-inflammatory diet, and sufficient intake of vitamin D play an important role in the prevention of attacks and worsening of MS, but without good medication, quality treatment is generally not possible. Biological therapy for the treatment of multiple sclerosis (MS) is also available for patients in Croatia, provided that they meet the criteria of the Croatian Health Insurance Fund. 

Although some patients have the opportunity to receive some of the biologic drugs that are significantly more effective than standard immunosuppressive therapy, unfortunately, many patients still do not have a satisfactory response. Additionally, although the safety profile of biologic therapy is generally better than standard immunosuppressive therapy, many patients also have side effects from biologic therapy.

Although we still do not know the exact cause of MS, new findings place great importance on the enhanced activity of the enzyme Bruton’s tyrosine kinase (BTK), which is present in patients with MS and is most likely responsible for the onset of nervous system inflammation. Namely, the increased activity of this enzyme enhances the activity of B lymphocytes themselves, which increase the production of antibodies and thus attack nerve cells. This mechanism of disease development is shared by several other autoimmune diseases such as rheumatoid arthritis and systemic lupus. 

So far, several drugs have been developed that block BTK activity and are primarily used in the treatment of lymphoma and leukemia. Although these drugs have so far been tested in the treatment of other autoimmune diseases and can potentially block the disease from the very beginning, none of them have come to life. The problem with previous BTK blockers is that they do not bind specifically to the highly active enzymes, but to all BTK enzymes present in the body. Namely, BTK is normally present in other tissues, and their blocking can cause harmful effects in terms of excessive suppression of the immune system, increased risk of bleeding, cardiac arrhythmias, and elevated blood pressure. This problem could be successfully solved by designing a special molecule that targets only BTK in B lymphocytes, the site of the main problem for patients with multiple sclerosis and some other autoimmune diseases. 

Not only do these molecules bind to the problematic BTK in B lymphocytes, but they bind to it 200 times more strongly, and thus the effect of the drug should be better than that of previous inhibitors. 

Healthy individuals who received this molecule in high doses as part of a phase 1 clinical trial did not have any side effects. Thus, the first safety problem of this group of drugs is solved, it will be exciting to see the effectiveness of this molecule in the treatment of multiple sclerosis and other autoimmune diseases. 

Neurologist DR. Hrvoje Budinčević is part of this exciting international project whose goal is to confirm that both targeted and strong blockade of BTK enzymes in B lymphocytes can achieve long-term remission of the relapsing form of MS. 

We are looking forward to a potential “game-changer” in the treatment of MS and that Croatian doctors and scientists are part of this project.

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Why is treating multiple sclerosis complicated and how this new treatment looks to solve these problems

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