[Vicky Karatzaferi] And now we welcome Mr Spyros Konitsiotis, who is a Professor of neurology at University of Ioannina and President of the Academy of Neuroscience, because we have some very important developments with regards to Parkinson’s (disease). Mr Professor, Mr President, good morning. Welcome to Alpha 989 and the ‘This is Alpha’ show.

[Spyros Konitsiotis] Good morning, Ms Karatzaferi.

[Vicky Karatzaferi] Before we talk about what is new with this revolutionary, as it seems, smart device, that you have developed with your partners, I would like to start with some introductory information regarding Parkinson’s disease, because there are a lot of questions. So, could you start by explaining to me, please, in simple terms, what it is about, because I think it is more than just the “trembling” that we associate with the disease.

[Spyros Konitsiotis] That is correct, it is not trembling at all. Trembling is something very simple. Parkinson’s disease is something much more complex. It is a disease of the brain. It is due to the destruction of nerve cells in the brain, for an unknown reason, which are slowly destroyed and die. These cells are unique, they do not reproduce, they do not replicate. Therefore, the loss of these cells causes serious problems. These cells produce a substance called dopamine, thankfully. So, we provide this substance externally with pills.
This deals with several symptoms of Parkinson’s disease, which we should state do not consist merely of a simple trembling, which is what most people think, but mainly a difficulty in movement. Parkinson’s disease means great slowness in executing motions; one becomes very stiff and slow. Their movements become more difficult.

[Vicky Karatzaferi] Can I ask something practical, since we mentioned mobility? Could it be a symptom of Parkinson’s when a person drags their feet and takes very short steps, as though their legs can’t bend?

[Spyros Konitsiotis] Certainly. If indeed their legs are stiff, walking cannot be correctly executed, their steps are short, and their feet don’t lift from the ground. The entire body is correspondingly stiff. And the arms. They are not as agile and quick as they were before. Tasks now take much longer to execute. That is the disabling symptom of the condition and it is managed quite well with drugs. However, as the years go by and treatment continues, the drug ceases to have a predictable effect over the course of the day.
So, patients fluctuate. After taking the drug, after an indeterminable period of time, the drug starts to act...

[Vicky Karatzaferi] What does “indeterminable period of time” mean?

[Spyros Konitsiotis] Sometimes it is 20 minutes, other times it is 40 minutes, sometimes it is an hour, and other times it never takes effect.

[Vicky Karatzaferi] Why does this happen? I do not understand, this happens, Professor, after years of using the specific regime?

[Spyros Konitsiotis] Exactly. Thankfully, it does not occur from the very beginning. So, we start the treatment by administering dopamine in pill form and, although at first the effect is continuous, smooth, throughout the day, subsequently, after several years of treatment, it starts to become briefer, in a way. It becomes somewhat unpredictable. In fact, when the drug does take effect, its duration fluctuates greatly at times it lasts 4 hours, other times it lasts 3 hours, other times 2.5 hours, and other times, as I mentioned, in advanced stages, one of the several doses patients take during the day may not take effect at all.

[Vicky Karatzaferi] Is it a degenerative disease?

[Spyros Konitsiotis] Yes, we call it “degenerative” because the nerve cells slowly die for an unknown reason. So, we call this process of death and destruction of nerve cells “neurodegeneration”. The other very common neurodegenerative disease is Alzheimer’s disease. Parkinson’s disease is the second most common.

[Vicky Karatzaferi] Regarding Parkinson’s, which we are talking about, what could this degeneration be related to practically in the clinical status of the patient? Namely, what are some of the things that are worse than trembling hands or not being able to walk correctly that could occur? Could they be bed bound?

[Spyros Konitsiotis] Unfortunately, yes. If the cells continue to die off without stopping, if we do not intervene with treatment, the symptoms become increasingly worse. Therefore, one’s movements could become so slow and rigid that they truly would not be able to move at all. This happened before the 70s, when dopamine started being used broadly as treatment, with the action of a Greek neurologist in America, Giorgos Kotzias.

[Vicky Karatzaferi] That is interesting information, I was not aware.

[Spyros Konitsiotis] Certainly. We should be proud of that.

[Vicky Karatzaferi] Definitely, certainly.

[Spyros Konitsiotis] He is the son of Mayor Kotzias, of Kotzias Square.

[Vicky Karatzaferi] Well, good genes indeed ((laughter)) and a great amount of effort and hard work, of course, because nothing comes from nothing.

[Spyros Konitsiotis] No, of course not.

[Vicky Karatzaferi] I would like to ask, Mr Konitsiotis. You said the progression of the disease could be dramatic and could lead to the patient being bed-bound, bed-ridden. I would like you to tell me what the first sign is, and, because we believe — rightly or wrongly — that Parkinson’s only affects the elderly, is it true that it could be encountered in younger people?

[Spyros Konitsiotis] Certainly. And at very young ages, too. The average age of diagnosis is 60, slightly higher in men. Despite that, it could appear at much younger ages, even below 30. In these very rare cases it is genetic in form, and is due to one gene. However, it does indeed usually start at around 60-62 or later. The symptom of the disease is not just tremor, as we said, which is the most innocent symptom. The main symptom is slowness of movement. People become progressively slower, inexpressive, stiff...

[Vicky Karatzaferi] Inactive, in the end.

[Spyros Konitsiotis] Indeed, very much so. Thankfully we have the treatment. The treatment, over time, starts to become unstable.

[Vicky Karatzaferi] I understand, it starts not to work as well as it did.

[Spyros Konitsiotis] That is our major problem. Because otherwise, everything would have ended here and we would be fine.

[Vicky Karatzaferi] Would you say that the starting age for the first symptoms potentially foreshadows the progress of the disease? I mean: When a person is, for example, 30 years old, which is rare and genetic in cause, or 60, they have — theoretically speaking and if all goes well — many more years ahead of them. When it appears to an eighty-year-old — regardless of the increase in life expectancy and the fact that older aged live better lives — does it mean that the progress of the disease will potentially be slower? Or is this disease like a “fingerprint” and, therefore, each case is unique?

[Spyros Konitsiotis] Clearly, each case is different. There is not one Parkinson’s patient in the world who is the same as any other.

[Vicky Karatzaferi] That is like a nightmare, isn’t it, Mr President?

[Spyros Konitsiotis] Yes, because we cannot carry out a good prognosis and prediction early on, regarding what will happen.

[Vicky Karatzaferi] So, isn’t there some type of preventive test? Is it hereditary?

[Spyros Konitsiotis] It is only hereditary in about 10% of cases.

[Vicky Karatzaferi[ So, we can’t be saved by taking a test to see if we will get it?

[Spyros Konitsiotis] Not at all. For now we are not saved at all, because — as you know — we cannot intervene in genes, for the time being. However, thankfully, gene therapies have already started and in the future that may be even more important. For the time being, we cannot prevent it. We can, however, begin treating it in time, and thus greatly improve the patient’s quality of life, because during the first years the drug is impressively effective.

[Vicky Karatzaferi] It is strong, effective.

[Spyros Konitsiotis] Very much so. Over time, however, it brings these problems. The drug still works, but its effect...

[Vicky Karatzaferi] However, this neurodegeneration impacts motion alone, from what I understand, or am I wrong? Does it also impact speech and thought?

[Spyros Konitsiotis] Speech is impacted indirectly, due to the overall slowness. One might speak slowly.

[Vicky Karatzaferi] Their speech?

[Spyros Konitsiotis] Exactly, just their speech however. Nevertheless, it is a disease of the brain. It is reasonable and correct, therefore, to assume that it impacts other functions which are not related to mobility, such as cognitive functions, neuropsychological functions...

[Vicky Karatzaferi] What does “neuropsychological” mean?

[Spyros Konitsiotis] We mean, for example, neuropsychological symptoms, the main one being depression.

[Vicky Karatzaferi] So there are comorbidities?

[Spyros Konitsiotis] Many comorbidities. Out of psychological comorbidities, the most common is clearly depression, which may precede the motor symptoms of the disease by 3 or even 4 years.

[Vicky Karatzaferi] How does this happen? Is it a result of the patient realising that they cannot complete simple daily movements, or is it one of the first symptoms anyway?

[Spyros Konitsiotis] It is one of the first symptoms of the disease and has a clear biological basis. Certainly, when the diagnosis takes place, with the mere diagnosis of a chronic illness itself the patient may exhibit depression due to this problem, like any chronic patient. However, Parkinson’s disease depression has a very clear and major biological basis, as well as other problems: cognitive, namely space comprehension, cognitive functions, which are problems that grow as the disease progresses and age increases.

[Vicky Karatzaferi] Let’s pause for a moment because we need to take a short break, and when we return I would like us to get to what is new and more hopeful. You can tell us about the device that contributes decisively, from what I read, to the management of the disease.

[Spyros Konitsiotis] That is what we believe.

SECOND PART

[Vicky Karatzaferi] We are here with the President of the Neuroscience Academy, Professor of Neurology at University of Ioannina, Mr Spyros Konitsiotis, discussing Parkinson’s disease. We analysed, Professor — would you like me to call you “professor” or “president”? What do you prefer?

[Spyros Konitsiotis] “Professor” is fine. In any case, everyone is a president of something in Greece, as you know.

[Vicky Karatzaferi] ((laughter)) True. Just like “you are whoever you declare to be”. That isn’t the case with you of course, but nevertheless. ((laughter)) So, we analysed the profile of the disease, we talked about the treatment with pharmaceutical regimes, and you explained this particularity of the drugs, from a certain point onwards they may not “work” well with the patient. However, you and your partners, whom I would like you to mention, have developed a device which — what does it do? It’s trendy to talk about smart devices, because they are smart. They can help patients remotely, correct?

[Spyros Konitsiotis] Exactly, they belong to the smart and wearable device category.

[Vicky Karatzaferi] I would like you to, very simply, tell me how long the research took and what made you decide to work in this particular sector of research, and then move on to how the device is actually used.

[Spyros Konitsiotis] Right. I mentioned the reason we started with this device earlier.

[Vicky Karatzaferi] The impasse with the drugs?

[Spyros Konitsiotis] Exactly. The drug solution fluctuates to such a degree during the day, that the physician, in order to soundly adjust the treatment, needs to know it. Thus, the physician will move the drug doses correspondingly and regulate their intensity throughout the day, in order to achieve better treatment. In order to do that, they need to know exactly what is going on. The patients and their caregivers often try to communicate this problem over the telephone, especially during the pandemic, and that is not achievable. The physician cannot have an image of how the symptoms fluctuate throughout the day and that creates an obvious gap.
So, on that basis and in coordination with professor of biomedical engineering and informatics, , Mr Fotiadis, at University of Ioannina, 15 years ago, we started this effort to create a device that can record easily and wirelessly — while also being wearable — all the symptoms of Parkinson’s disease and transmit them to the physician, wherever they may be, in a comprehensible way, so they can do their job. So, that was our long history. And now, almost 15 years later, we have the pleasure of this device being a certified medical device.
I think it is one of the very few — if not the only — medical device that was developed and is fully manufactured in Greece and is sent to countries all over the world.

[Vicky Karatzaferi] Are there comparable devices abroad? Or is this a step further, something more advanced, something new?

[Spyros Konitsiotis] It is clearly both the most advanced device, and also the device that provides the best quality of information for neurologists, in order for them to carry out the best treatment for Parkinson’s disease, far beyond any similar attempt.

[Vicky Karatzaferi] Do patients carry it with themor is it positioned through some sort of operation?

[Spyros Konitsiotis] No, not at all.

[Vicky Karatzaferi] Because we have heard of other neurodegenerative diseases for which there are certain operations that implant some microdevices...

[Spyros Konitsiotis] There is an operation in Parkinson’s as well, where an electrode is placed in the brain. That is an operation during which a hole is essentially opened in the patient’s head. That has nothing to do with us. Our device consists of sensors, monitors, which look like a watch and are worn very easily with a strap on the patient’s arms — one on one arm and one on the other — and on their legs — one on one leg and one on the other — and a fifth sensor is worn on the torso, on their belt, or placed in their pocket. These devices are like a watch and are worn with a band. They have no wires, no cables communicating between them, they have no buttons to press, they have nothing. As soon as the patient wears them they start recording and the patient is free...

[Vicky Karatzaferi] They are like step trackers, but they count symptoms. I am oversimplifying tremendously, just to help us understand...

[Spyros Konitsiotis] Exactly, it has many sensors inside, which record all types of movements and translate them through complicated algorithms, those called “machine learning”, and in the end they create a symptom report, mainly visual, which they transmit to the physician, who can view it on their computer, wherever they are in the world, in a very comprehensible way. Patients move normally, as they would do every day. They carry on with all their activities in their natural space, their home, or wherever else they are. That is very important, because we get to see them in their natural space.

[Vicky Karatzaferi] Also, often, they cannot travel if they are very old, so this solves that problem.

[Spyros Konitsiotis] Yes. Especially now, during the pandemic, this problem was exacerbated more than we expected; much more. So, therefore, the need for this device, especially in our era, is even greater.
Thus, patients do not need to come to a hospital, with all possible risks, especially patients who have difficulty to travel. Now we can see with exceptional precision and very vividly what is happening throughout the day, in relation to when they took their medicine, what medicine it was, what its result was on the patient. We see almost all the symptoms of Parkinson’s disease and then, very easily, the physician can, having a complete picture of what is happening, inform the patient and recommend the suitable change to their treatment. In this way, the patient’s treatment becomes much better, better than ever before.

[Vicky Karatzaferi] This device, do I dare ask what the cost is and whether it is covered by social insurance?

[Spyros Konitsiotis] For the time being it is not covered. In no country in the world, with the possible exception of Germany, where we believe that, in cooperation with the country’s new main insurance organisation, a large number of patients will be reimbursed. Not yet, in Greece. So the funding and cost differs from one country to another, naturally, and the way it takes place.

[Vicky Karatzaferi] So, I would like you to tell me, what are we doing in Greece? Are the patients burdened with the cost?

[Spyros Konitsiotis] The standard for all countries, in accordance with operational guidelines and availability, is for the device to be available to the patient, namely, the patient needs to acquire it.

[Vicky Karatzaferi] Where from? Directly from the manufacturer?

[Spyros Konitsiotis] Exactly. It is for sale and they can get it directly from the manufacturer, who can, of course, send it anywhere and show them the very simple method by which it is worn and how the batteries are charged overnight.

[Vicky Karatzaferi] Is there a cost for the physicianphysican? Do they download an application on their computer to monitor the patient?

[Spyros Konitsiotis] No, not at all. There is no cost for the physician and the symptom report can be easily viewed on their computer through an online application, which, of course, they log into with personalised passwords, as required, because it is medical information. The company complies with all personal data protection standards to a very high degree. So, the physician logs into this application and views, from anywhere where they have internet access, very easily, the results of each of their patients. Each physician may have many patients they monitor using this method.

[Vicky Karatzaferi] So, essentially, if they are being monitored by their physician, an older patient who is not familiar with smart devices, how will they understand what they have to do? Will they then speak over the telephone, for example, and will the physician explain things?

[Spyros Konitsiotis] Exactly. If the physicianphysician sees the report from the PDMonitor on his computer screen, he will understand and call his patient— often the patient calls asking — and recommend the suitable adjustment to the treatment. It is very interesting, after a specific period of time, when the patient wears the device again, so that the physician can be certain of his intervention’s results; another benefit of the device. Of course, there is no cost to the physicianphysician.

[Vicky Karatzaferi] Good. That is an important parameter and I wanted to resolve it, because I am sure that there are many people who are interested to know. But you didn’t tell me precisely what the cost is.

[Spyros Konitsiotis] I don’t know if we should be talking about the cost publicly. Patients can call or e-mail the company.

[Vicky Karatzaferi] Will they receive the information over the telephone or via e-mail?

[Spyros Konitsiotis] Certainly. The company is called ‘PD Neurotechnology’. The “PD” is from Parkinson’s Disease.
‘PD Neurotechnology’. There is a website for patient access with information, a telephone number that they can call and get the information on how they can acquire it.

[Vicky Karatzaferi] What other countries is it available in?

[Spyros Konitsiotis] It is already available in many European countries. It has not yet made it to America, we believe it will be available at the end of the year. Naturally, it is available in all European countries, because it is an international company. Slowly the device will be made available around the world.

[Vicky Karatzaferi] I would like you to tell me, as you researchers never stop searching and setting new goals, what is the next target and whether you have already started doing something new?

[Spyros Konitsiotis] Of course. We can expand its use. So far patients do not wear the device at night, during sleep. This was for practical reasons and because we had decided from the beginning to focus on daytime symptoms. There will be a version of the device that will record night-time symptoms, which are very interesting.

[Vicky Karatzaferi] So the patient presents symptoms while they sleep? They have tremors?

[Spyros Konitsiotis] Yes, they present symptoms during the night, several and different to those they have during the day, which are also problematic.

[Vicky Karatzaferi] Such as?

[Spyros Konitsiotis] What we call “restless leg syndrome” and periodic leg movements during sleep. It is a disorder called “REM sleep behaviour disorder”, where, generally speaking, one moves in their sleep in a way that is related to the content of their dreams.

[Vicky Karatzaferi] Is this a sign of Parkinson’s? Because it sounds like...

[Spyros Konitsiotis] No, don’t worry.

[Vicky Karatzaferi] I’m not worried, it just sounds familiar. I have heard of it happening to younger people who do not have Parkinson’s.

[Spyros Konitsiotis] It also happens to younger people without Parkinson’s. Nevertheless, it is very characteristic at older ages and in Parkinson’s disease.

[Vicky Karatzaferi] It is a little scary for the person sleeping next to someone suffering from it. I mean, waking up at night... I am joking, but I mean imagine seeing your partner moving as though they are living something in their dream, I think that is very scary.

[Spyros Konitsiotis] It is. Sometimes they may make sounds, too, it is unpleasant in general. It isn’t nice, at night. And the person next to them may be injured, the patient may strike them with one of their sudden movements.

[Vicky Karatzaferi] So, you mean, the movements may be violent?

[Spyros Konitsiotis] Very often the dreams we see are, unfortunately, violent and scary. We give chase or are chased, we try to protect ourselves.

[Vicky Karatzaferi] Don’t the drugs mitigate the symptoms during the night?

[Spyros Konitsiotis] Only a little, partially. Because the mechanism that exists in all of us of becoming paralysed when we see these dreams to avoid making such movements, does not work. In the framework of this disease the mechanism does not work.

[Vicky Karatzaferi] Right.

[Spyros Konitsiotis] So we make these movements, obviously related to the dream, which we normally shouldn’t make.

[Vicky Karatzaferi] So, the next stage, if all goes well, is night time, during sleep.

[Spyros Konitsiotis] Yes. We are creating one more version, which I think is very important, which will help physicians who are trying to control the stimulator, namely the device that we mentioned earlier, which, often, is the electrode placed in the brain in some Parkinson’s patients. That electrode, which is used in other cases, of course, requires external control, which is often time consuming and difficult. We believe that another version of the device will make it much easier to control the electrode, in terms of both duration and quality. But this is a research plan for the future, let’s not go into details now.

[Vicky Karatzaferi] We will have the opportunity at some point, when things move forward, to talk again.

[Spyros Konitsiotis] When things move forward. Why not?

[Vicky Karatzaferi] Thank you very much and I wish you every success.

[Spyros Konitsiotis] Thank you and I wish you the same.

[Vicky Karatzaferi] Congratulations on your achievement.

[Spyros Konitsiotis] Thank you, good afternoon.

Transcription: Glossima & Wehrheim