News in the treatment of multiple sclerosis in 2021 cannot but rejoice! According to scientists, multiple sclerosis can be cured with the help of a pregnancy hormone.
Every scientist dreams of finding a cure for all diseases. It is especially difficult to identify the cause of some serious diseases, which makes it difficult to find a cure for the disease.
Russian scientists, as a result of long and diligent research, have come to the conclusion that there is a pregnancy hormone that can possibly be used to suppress immune cells. They provoke the development of multiple sclerosis, as well as some other autoimmune diseases. This hormone is human chorionic gonadotropin.
Prognostic factors
According to recent news about the treatment of multiple sclerosis, the identification of new drugs that can treat highly active forms of the disease requires a reconsideration of both MS phenotypes and attempts to identify prognostic factors for the course of the disease.
An accurate description of the clinical course (disease phenotype) is important for communication, clinical assessment, and selection of effective therapy as soon as possible after diagnosis.
The International Advisory Committee on Clinical Trials of MS is revising the original descriptive characteristics of MS (based on increased knowledge about the disease and its pathophysiology). The purpose of the research is to re-evaluate the concept with an emphasis on disease activity and progression in accordance with the clinical picture and MRI findings.
According to the new concept (news for December 2021), the goal of treating multiple sclerosis is to achieve the so-called. NEDA (No Evidence of Disease Activity), the criteria for which have already been revised 4 times.
At the moment, there is a lack of an important indicator - a biomarker that clearly determines the course of MS. This does not allow personalizing treatment or monitoring its success.
conclusions
“Now that we know about these mutations that drive the biological process that leads to increased inflammation in MS in families, we can try to address its root causes,”
Vilarinho-Güell.
Researchers hope the study's findings will one day help develop personalized MS treatments and prevention strategies for those at greater risk of developing the disease.
The authors of another study claim that multiple sclerosis can be treated with an allergy drug.
New in MS treatment
The latest news in the treatment of multiple sclerosis (late 2021 - early 2021) is represented by 2 new products - oral Cladribine and the drug Ocrelizumab.
Oral cladribine was previously approved for the treatment of severe and highly active relapsing-remitting MS. These are the tablets used in courses:
- 1st year – 2 5-day courses with an interval of 4 weeks;
- 2nd year – a similar course with the same regimen.
So far, the effects of this treatment appear to be long-lasting. The mechanism of action of oral Cladribine is the selective depletion of B and T lymphocytes, after which the immune system is restored. No serious side effects were reported.
Based on Cladribine, the drug Leucovir will be released in Belarus by 2021.
Ocrelizumab is a drug that targets CD20+ B cells. Used by intravenous injection according to the following scheme: 1st injection → one-week break → 2nd injection → each subsequent injection after a 6-month break.
Indications for use of Ocrelizumab are a highly active remitting and progressive form of the disease.
Apart from the increased risk of infection due to the mechanism of action, the occurrence of significant adverse events is not yet known.
The safety of oral Cladribine and Ocrelizumab has been monitored in clinical trials, but real-world data are still insufficient.
Relevance of the problem
Multiple sclerosis (MS) is an autoimmune disease that affects more than 2.3 million people worldwide. The disease attacks the myelin located around the nerves.
As nerve function declines, a range of symptoms develop, including vision problems, muscle weakness, difficulty walking, and problems with balance and coordination.
Current treatment is aimed at preventing further damage, and no drugs can repair damaged myelin. The discovery of a drug that can repair damaged myelin would be a huge step forward. And according to the latest research, this could happen soon.
In 2014, research conducted by Professor Jonah Chan at the University of California, San Francisco, showed that the drug clemastine fumarate
may help treat MS. Clemastine fumarate was first approved in 1977 and has been available since 1993.
Xemus - Russian novelty
Xemus is a Russian medicine used for multiple sclerosis, and is now in the final phase of research. The mechanism of action of the new drug is based on a direct connection with the myelin sheath. According to studies conducted on this product, the effect is provided by the property of loading the peptide parts of myelin into liposomes.
According to the developers of the new medicine, it will be more affordable than previously used and modern imported drugs.
The estimated time of entry into the pharmaceutical market of this new product for the treatment of multiple sclerosis is 2019-2020.
Stem cells
Stem cells and multiple sclerosis are a combination that has provided solutions to doctors and hope to hundreds of thousands of patients around the world. This is the most anticipated news about the treatment of multiple sclerosis in 2018 - a period of important research in this direction.
The method is complex and includes several steps:
- selection of stem cells from the patient’s blood;
- effects on cells of drugs, including low doses of specific chemotherapeutic substances, immunosuppressants;
- returning the treated stem cells back to the patient's body.
The whole process is based on the fact that a sick person receives stem cells at a developmental stage that are able to adapt in the body, replacing nerve cells affected by the disease, restoring the function of the nervous system.
The results show that in the group of patients receiving stem cells, there were significantly fewer people with a relapse of the disease.
The specific numbers are as follows:
- within 2 years – progress in 2% of patients;
- within 3 years – progress in 5% of patients;
- within 4-5 years – progress in 10% of patients.
At the same time, 98% of patients did not experience worsening of the disease during the 1st year, there were no signs of MS, in 93% the asymptomatic state continued for 2 years, in 90% for 3 years, in 78% for 4 years. -5 years.
In the control group, which received standard treatment, the results were less optimistic:
- almost ¼ of patients experienced worsening of the disease within 1 year;
- more than ½ patients – within 2 years;
- the condition of almost ¾ of patients worsened within 5 years.
On the contrary, the percentage of patients without signs of disease and deterioration was only 40% during the 1st half of the year, 21% during the 1st year, 3% during 4-5 years.
Not all experts are so optimistic.
In 2021, the method was used on too small a percentage of patients, so conclusions may be premature. But this is one more step to suggest the right path, hope for patients who do not respond to any of the previously recommended treatments.
Bruce Bebo, executive vice president of the International Society for Multiple Sclerosis Research
Moskvich
About 9 thousand people suffer from multiple sclerosis in Moscow. Professor of the Department of Neurology, Neurosurgery and Medical Genetics of the N. I. Pirogov Russian National Research Medical University, Alexey Nikolaevich Boyko, told Olga Darfi about the risk factors of the disease and that over the past 20 years, the diagnosis of “multiple sclerosis” has ceased to be a death sentence.
We learn about multiple sclerosis only after our friends begin to suffer from this terrible disease...
I don’t agree with you, there is nothing terrible about this disease at present. Today, when treatment options for this disease have improved significantly, patients have a normal quality of life, good performance and longevity. Multiple sclerosis is possible and should be treated; this diagnosis is not a death sentence. The impression that multiple sclerosis is a “terrible disease” is created because those who fell ill with it a long time ago, for example 20 years ago, now have persistent disability and are more difficult to help. We don’t have any methods to “lift” them from the stroller. We do not have the ability to transplant the brain and spinal cord; science has not yet succeeded in this. But they can be helped with symptomatic treatment and rehabilitation.
Multiple sclerosis (MS) is a chronic disease of the central nervous system of predominantly young people. At the same time, due to autoimmune-inflammatory and neurodegenerative changes in brain tissue, various functions of the nervous system are disrupted. If the disease is not treated promptly and correctly, then these people have increasing problems in various functions of the nervous system (vision, movement, coordination, etc.), which leads to problems in self-care.
In Moscow there are about 9 thousand people suffering from MS, and more than 150 thousand in Russia. Unfortunately, the number of such patients is increasing, including in those countries and populations where it was previously rare or not encountered at all. MS is called a disease of civilization. Civilization came to Arab countries along with oil money - now they have more patients with this disease than in Russia. And yes, this is a disease of the urban population.
Why are there more and more such patients?
More active influence of external factors that affect individuals with a polygenic predisposition. Previously, it was believed that only Europeans suffered from this disease. There is a theory that the Vikings once spread the predisposition to this disease around the world, but today all ethnic groups suffer from MS.
External risk factors are certain viruses, toxic environmental influences, unfavorable ecology, lack of vitamin D, dietary habits, and smoking.
Are there early symptoms of the disease? What should an ordinary person pay attention to?
For any disorders of neurological functions - vision, movement, coordination, sensitivity (sometimes hypersensitivity, sometimes hypo-). Just don’t specifically look for “symptoms” in yourself or your relatives, otherwise it will be like Jerome K. Jerome, when the hero came across a medical encyclopedia and he found all the diseases in himself, except for puerperal fever.
I just have a visual impairment...
If there is a visual impairment, then you need to go to an ophthalmologist so that he can look and determine whether it is your peripheral apparatus or the optic nerve that is suffering. If it’s the optic nerve, then a neurologist will look into it. He was taught this for six years, plus residency. Otherwise, sometimes it happens in our country, as one wonderful humorist said, “the entire adult population of the country knows how to teach children, heal people and play football.” Therefore, it is better not to engage in self-diagnosis, much less self-medication.
That is, you need to go to a regular neurologist at the clinic?
If there is a violation of neurological functions, you can go to different medical institutions where there is a neurologist. There are regional, city and federal centers. But for patients with MS, in addition to the neurologist, there is a specialized service in the clinic, and this is the case all over the world. We created the Moscow City Center in 1998, now it is divided into five parts at large city hospitals. These are the so-called inter-district departments, because it is quite difficult to regularly monitor more than 9 thousand patients in one place.
There are good drugs, but they only work if they are prescribed accurately and correctly; there is no one “super-effective pill” that will immediately help everyone.
Specialized MS centers around the world are created by analogy with departments that provide care to patients with stroke (Stroke Unit), which have now been created in our country. The issue of the widespread creation of a special MS Unit (MS, multiple sclerosis) is being actively discussed, where comprehensive care would be provided to just such patients. So that these patients can be treated by multidisciplinary teams, because in addition to neurologists, they need psychologists, rehabilitation specialists, urologists, other doctors, and special nursing staff. We need specialists in clinical immunology, because all drugs act on the immune system, there must be competent neuroradiologists who understand MRI - it is impossible to make a diagnosis using MRI alone, a similar picture on MRI can be for many other different diseases, and you need to be careful in everything figure it out. MRI is very important in monitoring the effectiveness of therapy.
What is the diagnosis of MS?
There are internationally accepted criteria. In most cases, the diagnosis of MS can be made based on the typical clinical picture. We also use MRI data of the brain and spinal cord, neurophysiological, and laboratory methods, such as the study of cerebrospinal fluid, to supplement and confirm. But we must understand that the diagnosis of MS is a diagnosis of exclusion. The drugs that are used for MS are very specific; they only work if they accurately target the pathological process that occurs in the body.
But this is a very long time. It may take a long time for a person to have other diagnoses ruled out.
Why? The main clinical indicator is a criterion for the dissemination of a pathological process in brain tissue in space and time; this multiple chronic lesion, if other causes are excluded, can be caused by MS. There are different diagnostic criteria, but in the MacDonald criteria of the previous version of 2010, a month is allocated to exclude everything. Now, if you correctly collect anamnesis and all the studies, then the diagnosis can be made already at the first visit. In MS, the earlier the diagnosis is made, the more effective the use of drugs will be, because they prevent the formation of new lesions and symptoms.
I just came from Vladikavkaz. There is a large medical center in Beslan, the entire region gathered there - Chechnya, Stavropol, Dagestan and we are with them. In addition to new treatment methods, issues of differential diagnosis were discussed for many hours. There are good drugs, yes, but they only work if they are prescribed accurately and correctly; there is no one “super-effective pill” that will immediately help everyone. Well, it is also impossible to cure such a person forever today - we will not change the genes, they came to him from his mother and father, we can only improve the picture of the disease, and it will minimally bother the person.
What is the situation with early diagnosis of MS in Moscow?
There are enough tomographs, there are enough specialists working in all these district departments - these are graduates of our department, which is headed by Academician Evgeniy Ivanovich Gusev, all are students of our school. From time to time we hold educational seminars with them not only in Moscow, but throughout Russia; more than 25 schools have already been held in different cities, organized by the All-Russian Society of Neurologists and the Russian Committee for Multiple Sclerosis Research.
Now there is every opportunity to make a diagnosis on time. Only a neurologist should do this. Although we published the book for a wide range of people, specifically for patients and their relatives. There we tried to present in an accessible form everything necessary for non-professionals regarding diagnosis, medications and non-drug methods - gymnastics, diet, yoga, lifestyle, family planning, etc.
Excellent book, I even see a chapter on Ayurveda...
We tried to include everything, but our first chapter is about medications that have been tested using evidence-based medicine. They are used all over the world, please accept them. And at the same time, do hardening, take vitamins, whatever you want, the main thing is that it does no harm.
What has changed in the treatment and diagnosis of MS since the last century?
In Soviet times, a diagnosis of MS was a death sentence. The sick person became disabled, hence, as you said, stories about a “terrible disease.” And over the past 20 years, the life expectancy of people with MS has been almost the same as that of the general population. With the right selection of therapy, they remain able to work, play sports, perform on stage, give birth to children, no problems.
Progress in the treatment of MS has been recognized as the highest achievement of the “decade of the brain.” In 2013, we received an award from the Moscow government for the best work in the field of healthcare, when we first substantiated that certain drugs should not be prescribed to everyone, but should be selected individually. Twenty years ago, the first two or three drugs appeared, and now we already have 15 different methods that make it possible to change the course of MS and control it. They are called drugs that modify the course of MS, or DMTs. But the drugs must be used correctly, there are more active variants of the disease, and there are milder ones.
I know that treatment for MS is one of the most expensive in the world.
The state buys drugs for patients, yes, everyone without exception is entitled to. The Moscow government began purchasing drugs 20 years ago. At first there were 200 people, then 500, since 2005 there has been a federal program. Currently, about 60 thousand patients receive expensive drugs at state expense. If patent protection ends, then after clinical trials the original drugs are replaced with Russian, say, analogues. Last year, we included a new expensive drug in the government procurement list - the monochannel antibody alemtuzumab; this year we included ocrelizumab, which is indicated for patients not only with the usual relapsing course of the disease, but also for patients with the most unfavorable primary progressive course. For this option, there is only one drug available so far, and it will also be purchased by the state starting in 2021.
Will the government program for replacing foreign medications with Russian analogues affect patients with multiple sclerosis?
If it is proven that a drug has the same effectiveness, safety and tolerability, but is three times cheaper, then all over the world such a drug is replaced with an analogue. The drug has patent protection time. When it ends, analogues come out. The main thing is that they are well researched. Now, in accordance with regulatory documents, not a single analogue, be it domestic or foreign, is approved without testing.
Well, have they already prepared a replacement for MS patients with domestic analogues?
Yes, almost all beta interferons are Russian, glatiramer acetate, the experience of using them goes back more than 20 years. They have been proven to be safe, they have Russian analogues that have undergone good research, and they are used instead. Of course, monoclonal antibodies are newer and have patent protection, but Russian companies make their own drugs. For example, a study of Russian pegylated interferon and several monoclonal antibodies is currently underway. But the main thing I would like to note is that now there is a civilized approach, and not advertising of healers and miracle pills. Long-term studies are carried out using evidence-based medicine methods, the results are provided and treatment is planned based on this.
With the correct selection of therapy, patients remain able to work, play sports, perform on stage, give birth to children, no problems.
The fact is that the treatment of such patients is very variable and individual; there are no general protocols. For some the disease progresses this way, for others it is different, everything needs to be looked at and taken into account. For this purpose, specialized services and MS centers are being created throughout the country. The St. Petersburg, Samara, Kazan, Yaroslavl and Novosibirsk centers are very active. The stronger the biotech drug, the higher the risks. There may be somatic problems, infections may develop, etc. There is a drug, when using the first tablet of which it is necessary to monitor the ECG before and after taking it, and if you do not do this, you can get serious consequences. Each drug has a specific risk management plan called “pharmacovigilance”. If everything is done, then the risks are minimized. But there are no strong, effective and completely harmless drugs.
Is prevention possible?
You will not have any other genes. In Canada, they noticed that a lot of childhood MS had appeared, they immediately created a program for the disease and returned to vitamin D, but not as a prevention of rickets, as was the case in the USSR, but specifically to the prevention of MS. We also cannot particularly protect ourselves from viruses; here, perhaps, the fight for the environment can help. There are two factors that have been proven in large epidemiological studies that increase the likelihood of outbreaks of disease and the appearance of new symptoms. The first is any infection that triggers an autoimmune process, and the second is chronic psycho-emotional stress, which also affects immunoregulation.
Changes in the gut microbiome (for example, due to frequent use of antibiotics) also affect immunoregulation. Smoking clearly increases the risk of developing MS and worsens its course. Nutritional features - scientists noted that in many countries where the diet changed from fish to meat, there were more patients with MS.
Marijuana helps, I heard.
It simply reduces spastic muscle tone; this is one of the options for symptomatic treatment if this cannot be achieved by other methods. Such drugs are not allowed in the Russian Federation.
Is there a society for people with MS?
Certainly! Both the Moscow and Russian communities are very active, although their financial resources are not so great... I am a consultant to MS patient societies in Italy and Norway. Their organizations not only support patients, they finance scientific research. Now the Italian society, together with the European Charcot Foundation and with the support of the European Union, has launched a special program to evaluate the results of treatment by patients themselves. We are used to assessing the results of treatment how? The doctor looked at his scales, looked at the MRI device, EEG (ECG from a cardiologist), and a conclusion was drawn. But there has to be a third thing: patient-reported outcomes. It seems to be easy - I asked the patient, he answered, and sent the result. But the result depends on many nonspecific factors - mood, social situation, concomitant diseases. For example, before she or he filled out the questionnaire, there was an increase in blood pressure, which made the patient feel worse. This has nothing to do with multiple sclerosis, for the treatment of which a specialized drug is taken. Everything here is not as simple as it seems at first glance. The methodology is quite complex, it exists, it is being developed using devices. If a patient has a new complaint, is this an exacerbation? Or did he just have an argument with his boss at work? Large programs are written to monitor all this, your phone reads how you walk, movement coordination, balance. There are special short questionnaires that help monitor the patient’s condition.
Now you are in the new federal center. It was recently created, like the new department that I head, called the “department of neuroimmunology.” We deal not only with MS, but with all diseases where neuroinflammation occurs, and this happens in a wide variety of diseases, including stroke.
What is currently missing in Moscow in terms of social assistance and adaptation?
Thanks to the federal program 12 VZN, all DMT drugs are available, and new ones are included. But the big problem throughout the country is comprehensive rehabilitation, not only medical, but also social. More information is needed both about this disease and about the lives of patients. Some work is being done in this direction, but lagging behind the countries of the European Union and the United States. This center plans to place special emphasis on rehabilitation not only for stroke, but also for other neurological diseases, including multiple sclerosis, and this has many of its own characteristics. There are many directions for the development of all treatment methods, and it is gratifying that young doctors are very interested in this problem. Progress is visible, and I want to participate in a big thing and move on.
Photo: Alexander Lepeshkin
Monoclonal antibodies
Mouse, chimeric or humanized antibodies are used against various molecules, components of the immune system. But the potential benefits sometimes outweigh the toxic effects of the drugs. If substances that are not fully humanized are used, antibodies often form in the body. This leads to a lack of effectiveness of the product.
Although monoclonal antibodies have the disadvantage of being invasively administered, they are administered at longer intervals. Their disadvantage is the unexpected side effects of treatment when interfering with the fine network of immune regulation. On the other hand, selective intervention is more effective.
Many of these antibodies are used in hematology or in the treatment of other autoimmune diseases. Unfortunately, some of them are ineffective for MS.
Multiple sclerosis is a disease of the nervous system.
When it develops, immune cells push away the surrounding fiber sheath, called myelin. It is in its absence that the nerves stop working normally and conduct signals poorly, which entails various consequences. This may manifest itself in numbness of the limbs, loss of vision or the appearance of paralysis. As you know, today more than 2 million people suffer from this disease, and scientists have long been looking for a method to combat it.
As numerous studies have shown, human chorionic gonadotropin is one of the most important and necessary hormones of pregnancy. The placenta produces it after the embryo attaches to the wall of the uterus. It is this hormone that serves as the basis for the indicator of pregnancy, and it is used for the IVF procedure and the manufacture of medicines aimed at combating infertility.
All these facts prompted scientists to conduct experiments that showed that the hormone analogue is also suitable for combating autoimmune diseases.
This was a real breakthrough in science and instilled hope in the hearts of many people. Biochemists report that such a drug will be available on the market within a few years.
Litvinova Larisa from Kant University mentions the possibility of creating a medicine. As it turned out, the whole point is that human chorionic gonadotropin is aimed at modulating the immune system of a pregnant woman so that she does not experience feelings of aggression towards embryo antigens. In addition, this hormone copes very well with various types of infections. As you know, many people are constantly susceptible to various kinds of serious diseases. The cause of many diseases is not the effects of microbes and viruses, but the poor functioning of the immune system. As a result of the malfunction, its cells begin to repel good tissues, which leads to the onset of a serious illness.
Synthetic immunomodulators
BG00012 (FAE - fumaric acid ester) is a modified dimethyl fumarate molecule that is purer and has reduced side effects. The tablets have improved gastrointestinal tolerance. The drug affects T-lymphocytes, supports the alignment of the Th2 immune response with the production of anti-inflammatory cytokines. The drug activates the Nrf-2 pathway to protect cells from toxins, metabolic and inflammatory stress, and has a neuroprotective effect.
Approximately 10% of patients receiving BG00012 experienced elevated liver enzyme levels. The increase was 2-3 times higher than the upper limit of the standard, the indicators gradually returned to normal.
Complications occurred mainly when using the original liquid form of the drug. Now the drug is produced in capsules, which prevents its contact with the mucous membranes of the mouth, esophagus, and stomach. The medicine is not suitable for patients with stomach ulcers.
Typical side effects, occurring in more than 3% of treated patients, include:
- facial redness;
- body redness;
- feeling of heat;
- burning of the skin;
- increased sweating;
- headache;
- toothaches.
In addition, leukocytosis and cold symptoms have been reported.
It is recommended to plan pregnancy 30 days after stopping taking the drug.
Innovation and development in the current state
Today, research on the treatment of multiple sclerosis is being conducted in many directions. In addition to new immunomodulatory and immunosuppressive drugs, the effect is expected from monoclonal antibodies to individual molecules involved in various phases of the autoimmune process.
Antigen-specific treatments are also being tested (modified peptides, T-cell vaccination), and combination therapy is being tested. A successful but still experimental method is immunoablation with autologous stem cells.
The goal of most research is to search for drugs with regenerative and neuroprotective potential. New drugs provide greater effectiveness or effects comparable to modern drugs with new, often more convenient, methods of administration. But many new highly active substances carry the risk of unexpected side effects. Some of these complications are already known. Preparedness for them is a guarantee of timely diagnosis and the best choice of suitable therapeutic substances.
The ideal drug that controls the disease well enough, has no risk of side effects, and reverses the damage already done to the nervous system is all in the search stage.
