This time we are talking about the disease-modifying therapy (DMT), which according to most experts is one of the most important pillars in the treatment of people with multiple sclerosis. And I absolutely agree with this opinion.
In the best case, the disease-modifying therapy (DMT) prevents the inflammatory activity completely or slows it down at least strongly. Especially for the relapsing-remitting course of MS there are now a variety of therapies from mild to highly effective, depending on which intensity level is needed.
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Table of Contents
Introduction into DMT
Currently, you can’t really repair existing damage. The body can partially rebuild destroyed myelin at a young age, but not to the same quality as it originally existed. And the ability to remyelinate diminishes over time. In addition, at a young age remyelination and a higher inflammatory activity are opposed to each other. As a result, partially fresh remyelinated areas are immediately attacked and destroyed if the inflammation at the site has not yet come to a standstill but continues to smolder.
There are also initial therapies for the progressive forms of MS that can slow the progression. Here, the key disease process is neurodegeneration, i.e. the death of nerve cells, which unfortunately is not yet as well understood and treatable as the acute inflammatory activity. Researchers are working intensively on the subject. Other drugs are in phase 3 studies or are being investigated in earlier stages of development.
In an upcoming episode, I will share key advice and findings from research summarized in „Brain Health. Time matters in multiple sclerosis.“
This report was compiled by an international team of experts and is based on the analysis of a large number of studies on multiple sclerosis.
Understanding Multiple Sclerosis
Multiple sclerosis is a complex disease characterized by the patient’s own immune system mistakenly attacking the myelin that surrounds the nerve fibers in the central nervous system, protecting them and allowing particularly rapid transmission of stimuli.
This immune response leads to inflammation, demyelination, and scar tissue forms, disrupting the normal transmission of signals between the brain and the rest of the body. So far, the exact cause of MS is not known, but scientists believe that a combination of genetic, environmental and immunological factors play a role. MS symptoms vary widely from person to person. Fatigue, bladder dysfunction, numbness or tingling, muscle weakness, balance and coordination problems, cognitive issues, sexual dysfunction, and vision problems are particularly common.
The Role of Disease-Modifying Therapy (DMT)
Disease-modifying therapies, often referred to as DMTs or immunotherapies, are a category of medications used to treat and slow the progression of multiple sclerosis. Unlike symptomatic treatments that target specific symptoms, DMTs work by altering underlying disease processes. To do this, they suppress the abnormal immune system response, reduce inflammation and prevent further damage to the myelin sheath and nerve fibers. DMTs are a cornerstone of MS treatment because they not only relieve symptoms, but also help people with MS maintain a higher level of function and a better quality of life in the long term.
Types of Disease-Modifying Therapies (DMTs)
DMTs have revolutionized the treatment landscape for multiple sclerosis. They use different mechanisms of action to alter the course of the disease, alleviate symptoms and improve the quality of life of MS patients. In the following, we will take a closer look at the four most important mechanisms of these therapies:
1. Immunomodulation
Immunomodulating therapies are designed to regulate the immune system’s response in MS. They work by influencing the activity of immune cells and cytokines, which are signaling molecules involved in immune responses. These therapies help reduce inflammation and temper the immune system’s hyperactive response in MS. Examples of immunomodulating DMTs include interferon beta, peginterferon beta -1a and glatiramer acetate, all injectables.
Dimethylfumarat and Diroximelfumarat have an antiinflammatory and antioxidant effect and belong to the oral medications.
2. Proliferation Inhibition
Some DMTs target the proliferation of immune cells involved in the autoimmune response seen in MS. These medications slow down the division and replication of immune cells, reducing their numbers in circulation. Teriflunomid and Cladribin belong to this group and are both oral medications. Mitoxantron is given via infusion and nowadays only a back-up medication as it can’t be taken for a longer period due to possible severe side effects.
3. Migration Inhibition
Migration-inhibiting DMTs aim to prevent the movement of immune cells from the bloodstream into the central nervous system. This is crucial because it prevents these cells from entering the brain and spinal cord and causing damage. Natalizumab, an integrin receptor antagonist, is an example of a DMT that prevents immune cells from crossing the blood-brain barrier, thereby reducing inflammation. It can be administered as an infusion or injection.
Sphingosine-1-phosphate receptor modulators (S1P), trap certain immune cells in the lymph nodes, preventing them from entering the central nervous system and causing inflammation. Fingolimod, Ozanimod and Ponesimod belong to this group of S1P modulators and are taken orally.
4. Depletion
Depletion therapies take a more direct approach by targeting and reducing the number of specific immune cells. B-cell depleting therapies such as ocrelizumab and rituximab (only off-label) are well-known examples. They are administered as infusions. B cells are thought to contribute to the autoimmune response in MS. These therapies reduce the number of B cells and thus may alleviate inflammation and relapses. Alemtuzumab is not as widely used because of its potential side effects. Ofatumumab can be used independently at home as an injection after instruction.
Short summary on the types of DMTs
Each of these mechanisms of action represents a unique strategy to combat MS. They work in concert to alleviate symptoms, slow down disease progression, and enhance the overall well-being of individuals living with MS. The choice of DMT depends on various factors, including an individual’s specific form of MS, disease activity, and their response to treatment. Close collaboration between patients and healthcare providers is essential to tailor treatment plans to meet each individual’s unique needs and goals.
Another option is stem cell therapy, where the risk-benefit profile must be weighed very carefully. Based on current science, this treatment is only considered for a very selected group. I will talk about this option in a later episode.
Effectiveness and Progression Prevention
The effectiveness of disease-modifying therapies (DMTs) in preventing MS progression has been well-documented in clinical trials and real-world studies. These therapies have been shown to reduce the frequency and severity of relapses, slow down disability progression, and delay the accumulation of physical and cognitive impairments associated with MS. While DMTs are not a cure for MS, they are a critical tool in the management of the disease. Their effectiveness varies among individuals, and it’s essential to work closely with a healthcare provider to select the most suitable DMT based on an individual’s unique circumstances, needs, and goals.
Considerations for DMT Selection
Several considerations play a critical role in the selection of disease-modifying therapy (DMT) for the treatment of multiple sclerosis:
1. Disease Course and Activity
The choice of DMT often depends on the specific form of MS a person has. For relapsing forms of MS, more aggressive treatment may be considered, while for progressive forms, options are still limited and symptom management and control are the primary focus.
2. Individual Health Profile
The person’s overall health, including any comorbidities or pre-existing conditions, plays an important role in DMT selection. Some DMTs may not be suitable for individuals with certain health conditions or drug interactions.
3. Treatment Goals
Treatment goals may vary from person to person. For some people, the focus is on preventing relapses and new lesions, while others focus on minimizing the progression of disability. Still others want as little reminder of the disease as possible. In addition, depending on the region, there may be limitations on choice or only low-cost treatment might be available due to high deductibles. These individual goals drive the selection process.
4. Side Effect Tolerance
DMTs can have different side effects that may impact treatment adherence. It is important that you discuss your concerns and fears about possible side effects with your doctor. In the end, you should choose a medication that you are comfortable with and whose side effects are acceptable to you.
5. Monitoring Requirements
Different DMTs may require different monitoring measures, such as regular blood tests or imaging studies. These checks need to work for you on a day-to-day basis, as this is the only way to ensure safe long-term treatment planning. Often, there are more frequent checks at the beginning, which only need to be done at longer intervals later on.
Future Directions in DMT Research
The field of MS research is dynamic, with ongoing investigations into new disease-modifying therapies and innovative approaches. Here are some exciting areas of research that are forward-looking for DMT research:
Precision Medicine
Researchers are trying to find new biomarkers that can predict a person’s response to specific DMTs. This approach allows for more individualized treatment plans and increases the chances of selecting the most effective therapy for each person from the beginning.
Advanced immunotherapies
New immunotherapies are currently being developed that more specifically target immune cells and molecules. This should reduce side effects and increase efficacy.
Combination therapies
Researchers are exploring the potential benefits of combining different DMTs to achieve synergistic effects. This approach may allow for more comprehensive disease control.
Neuroprotection and repair
In addition to immunomodulation, research is focusing on therapies that promote neuroprotection and repair. These may include remyelination strategies and treatments to support neuronal health.
Patient-Reported Outcomes
Future research will prioritize patient-reported outcomes and aim to improve quality of life and functional abilities, rather than focusing solely on relapse rates or disability progression.
Summary of the future directions in DMT research
These innovative directions in DMT research promise to further improve the lifes of people with MS. As our understanding of the disease deepens and new therapies are developed, MS treatment is expected to become even more tailored and effective, which will offer hope for better outcomes and a higher quality of life.
I hope this gave you an overview about what a disease-modyfing therapy is, what advantages it offers in the long-run, what needs to be considered when choosing the right one for you and how future developments will increase our quality of life even more.
See you soon and try to make the best out of your life,
Nele
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