The latest immunomodulatory therapies implemented in the treatment of autoimmune and demyelinating pathologies are giving patients who were previously condemned to disability a chance at a normal life. However, with progress, new challenges arise for clinicians: the safe integration of the latest technologies into practice, the accuracy of diagnostics, and, most importantly, the correct delivery of evidence-based information to patients about lifestyle. Professor Marina Janelidze discusses these key issues in an interview with Medscriptum.
Against the backdrop of the continuous evolution of immunomodulatory therapy, confirmed by the start of a clinical trial for CAR T cell therapy for MS in Britain, what are the main challenges in integrating such therapies from clinical trials into widespread practice, particularly in ensuring long-term safety and real efficacy?
Immunomodulatory therapy has absolutely changed the lives of patients with Multiple Sclerosis (MS). I remember the period when these patients were practically condemned to disability. Since the mid-90s, after the introduction of immunomodulatory therapy, their quality of life has dramatically improved. These drugs modulate the immune system in such a way that the body is maximally protected from autoimmune reactions against its own antigens.
As for safety, every drug provided for immunotherapy goes through immense clinical trial “pressure” (Phase I, II, III A and B) before it reaches patients and widespread use. They undergo incredibly rigorous scrutiny throughout this entire period, resulting in a fully confirmed drug with positive effects reaching the patients. I would say even more: sometimes the effect and safety of immunomodulatory therapy for this disease are assessed for 5-10 years even after confirmation, to evaluate possible long-term side effects. Therefore, such fear is less likely.
On the other hand, there is no drug without side effects; such a drug does not exist in nature. I always repeat that the Georgian language has an unusual pair of words: “tsamali” (medicine) and “satsamlavl” (poison)—only our language has such richness to bring these two concepts so close. But believe me, as a result of clinical trials conducted in the West, these drugs are practically guaranteed to control side effects, although, I repeat, side effects can characterize everything.
Your report highlighted the importance of antibodies in predicting the outcome of the disease. Can you elaborate on the role of specific antibodies in assessing the outcome of neurodegenerative pathologies?
Previously, in neuroimmunology, there was a view that all similar diseases were simply “immunoactive pathology,” the first and so far most effective means of acute management of which is prednisolone (steroids).
However, with the growth of our immunocompetence, we now know exactly that one type of disease is caused by a specific antibody and a reaction to a specific antigen, while another is caused by a completely different type of antibody and antigen. This unified spectrum, which was considered one disease in my youth, is now so broken down into subtypes that their targeted treatment is no longer just a fantasy.
A time will come when we will know exactly that a particular spinal cord injury is caused by one immune mechanism or another, and accordingly, we will have precisely directed therapy. This is an event of enormous importance for medicine.
However, I want to sincerely note that Georgia is still far from this progress. We have information and knowledge about these innovations, but unfortunately, in reality, these latest approaches and therapies are not always accessible to our population.
In the management of inflammatory-demyelinating diseases (steroids in the acute phase, then targeted therapy), how relevant is the issue of drug resistance? Are there parallels between the immune resistance in oncology and the decrease in therapeutic efficacy in neuroimmunological pathologies?
Let’s compare it this way: oncology is a more “popular” field because it covers a much larger number of patients. In the case of immune-inflammatory damage to the nervous system, we must separately highlight Multiple Sclerosis (MS), which has also become quite “popular.”
As for other diseases, especially inflammatory-demyelinating pathologies of the spinal cord, there is less data on the possible side effects of targeted therapy even worldwide. This is due to the fact that these diseases are rare. Therefore, we do not really have such rich information on this issue.
However, the search for new immuno-targeted therapies is ongoing. I hope that as the number of confirmed and known diseases caused by immune mechanisms increases, new drugs that precisely suppress this target will definitely be developed against them. But to say that this arsenal is as rich as in oncology and multiple sclerosis—definitely not. Let’s see what the future holds.
How does the development of biomarkers and advanced neuroimaging methods change the diagnostic approach, and how important is their role for the early detection of neuropathologies?
In reality, the abundance of high-tech MRI (3 Tesla) machines in clinical practice is not a problem; on the contrary, we have so much of this technology here that we probably have more than we actually need.
However, as for biomarker research, the situation here is quite limited. This is due to the fact that relevant laboratory testing is expensive, and as far as I know, biomarker research is rarely done in our laboratories in Georgia. If it is done at all, its cost is so high (an astronomical amount) that patients, given that it is not state-funded, refuse the procedure.
Unfortunately, it is much easier to get a 3 Tesla MRI here than to have crucial diagnostic biomarkers tested.
Against the backdrop of the gut-brain axis research, how important is the dysregulation of the gut microbiome in the development and clinical manifestation of Multiple Sclerosis?
The brain microbiota is a very current and major topic in medicine in general. What we eat and consume goes not only to the brain but to the whole body. That is why this topic came into “fashion” in recent decades, because different countries, depending on their diet, are characterized by different endemic diseases. With respect to the brain, this issue is particularly important.
However, in terms of Multiple Sclerosis (MS), there is no very targeted research that will tell us exactly that this product can be consumed and that one cannot. On the other hand, I want to tell you that such dietary restrictions sometimes have a negative psychological effect on people. We should simply eat healthily.
Healthy eating means a standard: less fat, fewer carbohydrates, and more vegetables. Trust me, if we follow this standard, the risk of developing all diseases will be reduced. We do not need to scare people unnecessarily and, I will say in quotes, some kind of “terror” on this issue. This applies to both pharmaceutical companies and the constant discussion about what we can eat and what we cannot. Unfortunately, many young people are completely obsessed with this “overly healthy” diet, and I say unfortunately because this already exceeds the norm and does not allow for a life; they are always too much in order. Order is always good, but in my opinion, youth should also be characterized by a little “disorderly life.”
