3 Ways To Make Treatment With New MS Drugs More Effective and More Tolerable
21 January 2020
New MS drugs are the results of the latest scientific achievements in understanding the mechanisms of multiple sclerosis development. Stem cell therapy represents the potent support for modern treatment approaches.
Introduction
Treatment of multiple sclerosis (MS), a chronic autoimmune disease of the central neural system which may lead to a patient's disability, is still a challenge for the medical and scientific community. None of the existing approved MS treatment is an all-over cure, although each of them demonstrates effectiveness. MS medications are unable to completely prevent the recurrence of symptoms and the effectiveness of the available therapies is inversely proportional to safety, i.e. frequency and severity of its side effects, which is one of the most common reasons why patients with multiple sclerosis discontinue therapy [1].

In this article we discuss 3 approaches to make MS treatment more tolerable for patients through:
  1. Therapy Adjustments
  2. Adverse Reaction Management
  3. Symptom Management
Therapy Adjustments
Disease-modifying therapy (DMT) is the first treatment in the triad of comprehensive MS management. It modifies the disease course by reducing inflammation and damage in the central nervous system. It also decreases the number, duration, and severity of relapses (attacks). They are intended for long term use.

This year, the array of DMT medications approved by the FDA was replenished with 3 new medications – siponimod, cladribine, and diroximel fumarate. Their effectiveness varies from 46% to 56% [2].

Ozanimod is under review by the European and US agencies and is expected to be approved in 2020. The following substances are at the latest stage of their clinical trials and may be launched in the coming years:
  • laquinimod
  • ublituximab
  • ponesimod
as well as several others.
Picture 1. In 2019, three new drugs were approved for multiple sclerosis. It is expected that one more medication will be approved by the FDA in 2020.

Adherence to treatment plans ensures successful disease control. However, many people drop their DMT after a while because of the side effects. Among the most common adverse reactions of DMT are gastrointestinal problems, nausea, infections, and liver impairment. There are also special warnings and precautions listed by a national healthcare regulatory agency (FDA in the USA, EMA in Europe) for every MS drug (see Table 1).

Table 1. Adverse reactions that might occur during treatment with the currently licensed medications for multiple sclerosis [3].
Oral and infusion therapies approved by the FDA and EMA in the latest years are much more reliable and sustainable in their multiple sclerosis control, however, the safety profile is not fully determined for some of the newly approved medications (see Table 1).
Adverse reactions management
For all approved DMTs, clear indications and patient management plans are available [5]. The plan outlines measures to prevent and/or treat adverse reactions during MS therapy.

For example, a class-specific flu-like syndrome associated with IFNbeta can be managed through initial dose-escalation and the administration of analgesics and antipyretics, prophylactically or symptomatically [5].

For timely detection of liver problems and lymphopenia, physicians prescribe regular blood tests every 3-6 months of treatment.

Due to the potential of some MS medications to cause cardiovascular side effects (e.g., bradycardia, AV-block, and hypotension), US and Europe health agencies advise continuous electrocardiographic monitoring before the start of treatment and during the first 6 hours [6], [7]. In addition, there are specific warnings for patients with concomitant cardiac disorders or specific concomitant treatments (e.g., certain antiarrhythmics or beta-blockers).

To avoid risk to a fetus, women of childbearing potential must use effective contraception during and for 2 months after stopping MS treatment.

Progressive multifocal leukoencephalopathy (PML), though rare, may provoke severe disability or even death. It is usually caused by Human polyomavirus 2, also known as JC virus. Normally, it may exist in the body without any symptoms, however, when the immune system is suppressed by DMT, JC virus reactivates resulting in PML. The presence of JC virus and the relative risk of PML may be revealed by a specific and sensitive serum anti-JCV antibody test. When the JC virus is revealed by the test, it means a higher risk of developing PML. The result of the test helps the doctor to choose DMT medication or to switch to another DMD.

A consideration of the risks versus the benefits is taken into account when the treatment plan is created by the physician and patient together, so any undesirable condition should be discussed with the doctor. In the case of unbearable reactions, the physician can either adjust the treatment scheme and/or recommend supplemental therapy to mitigate adverse reactions.
Management of Symptoms
The nature of the disease causes impairment of various functions depending on the area where neurons are damaged. The may affect motor activity, balance, vision, memory, and thinking. Common symptoms faced by patients with MS include:

  • Problems with balance and dizziness
  • Tremors
  • Spasms and stiffness
  • Fatigue
  • Pain
  • Speech and vision deterioration
  • Bladder and bowel problems
  • Swallowing difficulties
  • Cognitive function decrease
  • Sexual dysfunction [8]

Ongoing management of MS symptoms involves both medications (which are selected according to actual patient's complaints) and nonpharmacologic support presented by several approaches.
Physical Therapy
Patients are usually recommended physical and occupational therapy as a part of the comprehensive approach to MS treatment. These supportive treatments help to alleviate pain, spasticity, and fatigue. Treatment also deals with speech and swallowing problems and helps improve overall physical strength and daily activity [9].

The following physical therapy may be recommended by physicians:
  • Xenon gas rehabilitation therapy (inhalation procedure)
  • Mesodiencephalic modulation (MDM)
  • Electrical myostimulation
  • SIS (super inductive system)
  • Oxygen therapy
  • Virtual reality
  • Kinesiotherapy
Exercises
There are several reasons why people with multiple sclerosis should adhere to regular exercise regardless of the medications prescribed for their disease. The exercises support drug therapy due to:

  1. Management of fatigue and spasticity
  2. Improved cardiovascular health
  3. Improved balance and coordination
  4. Mood control
  5. Regulation of the immune system at the cellular level
  6. Reduced inflammation [9], [10], [11], [12], [13], [14], [15].
Exercises are effective for patients with different levels of mobility and are a key element of successful coping with disease progression and coping with their symptoms.
Picture 2. Exercises and physical activity is a key factor in multiple sclerosis management.
Complementary and Alternative Therapy
Many people use complementary and alternative therapies together with conventional treatment recommended by a physician, or instead of it in the case of poor efficacy and/or intolerable side effects [18], [19]. Among diverse complementary and alternative treatments used by patients with MS, only a few have confirmed their efficacy to manage symptoms in evidence-based studies. These include reflexology, magnetic therapy, cannabinoids in various forms and Ginkgo biloba. These treatments are able to modulate pain, spasticity, paresthesia, urinary problems and fatigue [18].

Other treatment methods, such as diet, body-based and mind-body practices, as well as multiple biologically active substances and herbs (even when liberally applied) have an insufficient scientific base to measure their reliability.
How Stem Cell Therapy for Multiple Sclerosis Helps Patients Feel Better
Picture 3. Through the excretion of soluble factors, mesenchymal stem cells (MSCs) promote neuroprotection and immune system modulation [20].

Current approaches to regenerative medicine can contribute to all of the ways listed above to make MS treatment more effective and tolerable. Several studies have confirmed the immunosuppressive characteristics of mesenchymal stem cells (MSCs). They produce soluble biologically active molecules (growth factors, anti-inflammatory factors, etc.) that suppress the division of immune cells involved in neuronal damage that slows down MS progression and can even reverse the symptoms [21], [22], [23], [24].

Studies on experimental models of multiple sclerosis also confirmed the ability of mesenchymal stem cells to defend nerves directly via induction of neurogenesis and promotion remyelination [25], [26], [27], [28] [29] .

The efficacy and safety of stem cells derived from bone marrow were also shown in an increasing amount of studies, [30], [31], [32], [33], [34], [35], [36], [37].

Based on the ability of bone marrow-derived mesenchymal stem cells to reduce inflammation in the neural system, promote differentiation of neuronal cell progenitors, and stimulate the regeneration process in injured areas in the central nervous system, they are the promising tool which can be combined with existing and new drugs to reach long-lasting advantages for patients with MS [25]. Stem cell treatment may become a well-integrated part of comprehensive MS management due to their ability to act both on the level of coping with the disease and treatment of symptoms.
21 January 2020
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