Alzheimer Germany (AD): Prof. Citak, you have now been working for over a year with the device for the implementation of transcranial pulse stimulation, so the TPS. How did you come across the TPS, which is only – if we consider it in the time intervals in medicine – still very young?
Prof. Citak: I have been involved in regenerative medicine and traditional Chinese medicine for ten years. In regenerative medicine, focused shock wave therapies currently represent one of the best-studied therapies anywhere. There are now over 3,000 clinical studies on shock waves in medicine. Since we are one of the largest centers for shock wave therapy in Germany, we were therefore offered Transcranial Pulse Stimulation after its CE approval as one of the first practices ever. This was very convenient for me at the time, as a family member had just been diagnosed with Alzheimer’s dementia. I then said, ‘get me the device as soon as possible!’ If it helps just 2% as well as the other indications I treat with shock wave, I’ll be very happy already’. When I ordered the device, I never thought that we would be treating people other than my loved ones and that we would far exceed this targeted 2%.
AD: As a specialist in orthopedics with a professorship at the Hannover Medical School, you have been working with shock waves for many years and many people know shock waves just so far only from orthopedics. Often there is ignorance and uncertainty – what are shock waves at all?
Prof. Citak: A shock wave occurs when a body moves faster than sound. When an airplane flies through the sound barrier, it creates a shock wave, just as a lightning strike creates a shock wave, which we then hear as thunder. A shock wave is an acoustically audible wave, so we also call it a sound wave. The shock wave transmits energy in the range from infrasound to ultrasound without destroying biological tissue. When shock waves with very low energy are generated – which is what we do in transcranial pulse stimulation – so-called mechanotransduction occurs, i.e. the conversion of these physical signals into intracellular molecular processes. Simplified, one can say that the special TPS shock waves trigger a mechanical stimulus and this then leads to a biological response of the organism that initiates regeneration mechanisms.
AD: So now the shock waves have arrived in the field of Alzheimer’s dementia and other neurophysiological diseases, soon, by the way, also in cardiology, as one hears from professional circles. What distinguishes these shock waves in TPS from the other shock waves?
Prof. Citak: There you are somewhat wrong, shock waves have been used in cardiology since 1999! However, there are hardly any centers for the cardiological shock wave device MODULITH® SLC, which acts with specific focus on ischemic areas of the heart muscle. In this process, blood flow and metabolism are really significantly and permanently increased through the formation of new capillary blood vessels. It’s a great therapeutic method! But I think the problem in cardiology is that in this area many diseases are usually detected too late, namely when it is already too late and only a stent can provide relief. In the field of neurological indications, there is unfortunately no such effective intervention as with a stent in the heart.
There is no “plan B” here. That is why TPS therapy is so interesting in neurological diseases. TPS therapy is ultimately focused shock wave therapy, which we already know from orthopedics, cardiology and urology. There are only two differences: in TPS, the shock waves are applied at a very low frequency and are ultra-short, so that they cannot heat the tissue in the body, in this case the brain. In addition, the device we use for TPS has computer navigation built in, where you can follow the therapy process completely in real time on the screen and also see how the entire brain is activated evenly. Furthermore, the settings in the TPS system are preset for the brain and are almost impossible for the user to change. So you can’t do much wrong with this treatment.
AD: With the TPS we can penetrate through the skullcap about 8 cm deep into the brain. Simplified, we can thus reach the entire brain area of a person in the approximately half-hour treatment. What is happening in the patient’s brain?
Prof. Citak: As I said earlier: The shock wave represents a mechanical stimulus for the cell and this in turn reacts with a biological response. There is an increase in permeability, the permeability of the cell walls, and ion channels are stimulated, which are mechanosensitive. Incidentally, these ion channels form the basis for sensations such as touch, among other things, and are responsible for balance. Furthermore, nitric oxide is released, which leads to increased blood vessel dilation and thus an increase in blood flow.
The metabolism in the cell is boosted. By the way, many patients often feel these effects from the fourth or fifth treatment. The goal of TPS therapy is adult neurogenesis, which is also triggered by the activation of several growth factors, such as vascular growth factors. Adult neurogenesis refers to the formation of new neurons. This occurs primarily in the hippocampus, an area of the brain that is important for learning and memory processes. We achieve this with the shock waves of TPS (Editor’s note: see also “neurogenesis“).
AD: Professor, we want to point out explicitly at this point that the TPS stimulates the brain, but nerve cells need their time to regenerate. Many people then expect immediate miracles, that is, my husband, my wife, my mother, my father and so on is treated a few times with the TPS and then I want to see please also immediately results. We know that there are indeed such cases again and again. But this is not the rule. What do you say to the relatives and patients?
Prof. Citak: The biggest problem with TPS therapy is actually the short-term expectation of the relatives. What we can in no way promise is that TPS is a universal fountain of youth and that the brain is restored to a state of 20 or 30 years ago. Even shock waves can’t do that. The regeneration of the brain by TPS treatment usually takes at least three months, which means that the therapy triggers the brain cells, so to speak, but the expansion of new nerve cells, the formation of synapses, i.e. the creation of new networks in the brain often takes place mainly in the period after the initial series of six treatments.
We have some patients who report improvement only three months after the actual therapy. Of course, there are also many who experience significant improvements in a wide variety of areas already during therapy or shortly thereafter. We must not forget that the goal of therapy is primarily to stabilize and stop the disease. Improving symptoms is, of course, everyone’s goal and desire, including mine, but medically it is to be considered a secondary goal and the icing on the cake, so to speak. I have now spoken to patients who were treated a year ago and who, in retrospect, are very glad they did the therapy, although they were initially disappointed because there seemed to be only minor improvements at first. But weeks or months later, the change took place.
In retrospect, they realize that at least the actual condition at that time could be maintained, usually even more, of course, and that the disease would have progressed much further without the TPS. We communicate all this very clearly in the run-up to the treatment. Here we also have the great task of motivating the relatives to have a little patience. We do not focus on the short-term “aha” effect, but on the regeneration period and the time afterwards, which should and can enable the patient, and thus also the relatives, to have a better quality of life in many areas, as we experience time and again.
AD: Of course, we also get requests again and again, where it is about really advanced dementia diseases. The people hope then on the fact that one can make with the TPS perhaps nevertheless still something. How do you react to such requests and at what point do you say, “no, unfortunately we can’t help there anymore?”
Prof. Citak: Of course, there are also limits to TPS. But we have already had cases in which a patient had ultimately already progressed beyond the moderate dementia, so was moving towards severe dementia. Here, a factual, but above all also individual consideration is necessary and a clear discussion with the relatives. Since TPS therapy first and foremost does no harm, we can also try to improve the condition of someone who, for example, already has very severe orientation and word-finding problems. We also succeed time and again with amazing results, and we see time and again what feats the human brain can accomplish when it receives the appropriate stimulation. It is simply a balancing of many factors, which I cannot go into here in general terms. The boundaries are fluid and one must always consider the individual case. In general, I do not think much of generalizations. Every person and every medical history is different.
AD: The TPS will certainly be used in other indications in the future, because many neurological diseases are based on disproportionate cell death or plaque formation or even inflammation of the myelin sheaths such as in multiple sclerosis. Your colleague Dr. Henning Lohse-Busch, the developer of TPS, sees possibilities here not only in Parkinson’s disease, multiple sclerosis, and post-stroke conditions, but also in the treatment of polyneuropathies, incomplete paraplegia, Tourette’s syndrome, and also in coma vigil patients. How do you see it?
Prof. Citak: I absolutely agree here with my colleague Lohse-Busch. We know per se that all these diseases can be treated with shock waves. This results from their mode of operation and the logic or scientific knowledge accordingly out. But we can’t just start treating them here! Even if it is regrettable, here still much research must be done, still many studies must precede this. And these studies must be double-blind, randomized and placebo-controlled. Unfortunately, this takes years, but it is necessary. By the way, it is much more difficult in medical technology than in drug research. With drugs, for example, you can simply give the study participants tablets; they all look the same, no matter what’s in them. But here? We work with devices that generate the shock waves. These make, quite clearly, they are sound waves, noises, the device itself hums when it is switched on. So, if you want to do a placebo-controlled study, you have to use devices that are appropriately conditioned to be able to trigger an effect one time and not the other. This is possible, it is done, but it is very complex, time-consuming and very, very expensive. But with regard to the therapy of Parkinson’s disease, this will soon be the case. (Editor’s note: Two of these studies will be published in the fall of 2022).
AD: Keyword Parkinson. The many years of studies that are just coming to a conclusion give great cause for hope that we will finally be able to help these patients. You and your team are already working with TPS in Parkinson’s – as a so-called off-label therapy, which is already allowed. What is your experience?
Prof. Citak: In the meantime, we have already treated 40 patients as part of the “off-label use” and an observational study. Parkinson’s will be the next big step in TPS therapy, no question. Parkinson’s is a multi-faceted disease that is associated with more than the familiar physical impairments such as motor disturbances or a tremor, or shaking. Above all, the patients’ psyche is also extremely out of balance because not enough dopamine can be produced in the brain anymore. Here we have already had very good experiences and already some patients who are happy that the fears and the psychological imbalance disappear. This is an enormous piece of quality of life and also freedom that the TPS can bring about here. And also walking can become easier again, the tremor can be reduced. But we are still at the beginning here, I hope that in half a year I will be able to report from more patients in our own studies.
AD: Professor Citak, thank you for this interview and we look forward to further reports from you.