# Get the LATEST Research From Tass Lab

Parkinson's Community Los Angeles2023-12-07

Parkinson's#Parkinson's disease#PD#CR Stimulation#Tass Lab#Parkinson's Research

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ðŸ’« Short Summary

The video discusses neuromodulation techniques for treating Parkinson's disease, emphasizing deep brain stimulation and coordinated reset stimulation to desynchronize abnormal neuronal activity. Non-invasive rhythmic stimulation shows promise in long-lasting effects. Pilot studies on patients with Parkinson's demonstrate improvement in motor function without medication. Virotactile treatment and glove systems have positive outcomes in balance and shuffling symptoms. The focus is on personalized stimulation patterns and FDA approval for accessible treatment. Collaboration among researchers is crucial for future development in neuromodulation approaches for neurological conditions.

âœ¨ Highlights

ðŸ“Š Transcript

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Neuromodulation techniques for treating neurological conditions like Parkinson's disease.

01:16Dr. Peter Tas emphasizes inducing long-lasting relief by stimulating the brain to unlearn abnormal activity patterns and change connectivity patterns.

Different neurons serve different purposes and excessive synchrony negatively impacts brain functioning.

Deep brain stimulation is a significant milestone in Parkinson's treatment, with a patient demonstrating benefits.

The video segment showcases the use of electrodes and implantable devices for deep brain stimulation.

âœ¦

Limitations of deep brain stimulation treatment.

05:24Treatment may not effectively address all symptoms, such as gait balance and speech issues.

Approach aims to counteract abnormal neuronal synchrony by desynchronizing it.

Desynchronizing stimulation can lead to a decrease in synaptic connectivity.

By disrupting coherent structures in discharge patterns, a move from a pathological state to a healthier state may be possible.

âœ¦

Coordinated reset in deep brain stimulation for restarting rhythmic activity in neurons.

10:00Gentle stimulation helps neurons reduce synaptic weights and reset connections.

Technique involves a mix of periodicity and randomness for physiological information processing.

Mptp neurotoxic substance severely impacts dopamine production and motor functions in monkeys.

âœ¦

Results of Coordinated Reset Stimulation on Monkeys and Parkinson's Patient

15:25Monkeys stimulated externally for two hours with coordinated reset stimulation showed no difference in movement production rate compared to normal monkeys.

Patient with Parkinson's and dystonia experienced improvement after CR stimulation, with symptoms disappearing after one month.

Standard deep brain stimulation was less effective for dystonia than CR stimulation.

Unilateral stimulation showed persistent effects even one hour after stimulation was turned off.

âœ¦

Non-invasive treatment through rhythmic stimulation of neurons has potential with effects lasting up to 4 hours.

17:30Manipulating the timing of neuron populations led to significant outcomes in patients with various conditions.

Stimulation of thalamus regions like the ventral cordal nucleus produced rhythmic responses tied to external stimuli.

This method, known since the 1980s, offers promising possibilities for long-lasting effects without invasive procedures, such as vibrating gloves.

Studies by neurosurgeons have provided valuable insights into understanding neural responses and optimizing treatment approaches.

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Importance of Entrainment in Brain Stimulation.

21:55Neuronal discharges must be timed properly for effective brain stimulation.

Changing neural networks is essential for learning.

Fingertips are targeted for stimulation due to their large cortical representation.

A non-invasive glove system with vibrators shows promising results in pilot studies.

âœ¦

Study on motor function improvement in patients without medication.

24:52Patients in the study had to withdraw medication for 12-48 hours before exams.

Significant improvement in motor scores was observed even without medication.

Long-term effects were encouraging, with patients showing improvement after being off medication.

Study aimed to determine clinically significant effects using MCI, with a decrease in motor score greater than 3.25 deemed significant.

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Clinical improvements and reduced medication seen after 3 months of GL therapy for Parkinson's disease.

29:20Significant decrease in Parkinson's related abnormal brain rhythms observed post-treatment.

Lasting benefits up to 1.5 years post-treatment reported in patients.

Promising results from the therapy, but further research needed to validate findings against placebo effects.

âœ¦

Virotactile treatment shows significant improvement in Parkinson's patient.

35:04Patient experienced reduced medication, improved motor functions, and enhanced sense of smell and taste.

Patient was able to return to work, run the New York Marathon, and participate in a Triathlon.

Case study emphasizes potential benefits of virotactile treatment for Parkinson's patients, showing unexpected improvements beyond motor symptoms.

Future studies will focus on systematically studying these additional benefits.

âœ¦

Patient showed significant progress in walking stability after six months of treatment.

40:00Treatment involves a glove system and deep brain stimulation, showing favorable effects in patient response.

Investment in optimizing treatment and upcoming pilot studies for different patient populations.

Focus on improving motor symptoms and overall patient condition through innovative technology and research.

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Research aims to provide personalized stimulation patterns for patients through mathematical models that mimic brain activity.

42:48Pilot studies are being conducted to optimize treatment and prepare for larger scale studies.

Timeline for FDA approval and reimbursement is dependent on achieving substantial goals with competent team members.

Focus is on providing professional and accessible treatment to as many patients as possible.

Emphasis on thorough testing and minimizing risk factors for successful implementation.

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Importance of conducting placebo control trials for sensory treatments.

46:32Initial pilot studies and proof of concept trials are planned before FDA approval trials begin.

Goal is to provide treatment to all patients quickly, focusing on analyzing relaxing effects psychologically and through brain recordings.

Device may be usable for BBS patients, with no apparent reason for it to not be feasible.

âœ¦

Conducting pilot studies is essential before larger trials for testing treatments on patients with conditions like Parkinson's Tremor and essential tremor.

51:34FDA approval is crucial in the process of testing treatments on patients with neurological conditions.

Promising results have been observed in early studies, particularly in non-motor symptoms.

Lack of networking among researchers using vibratory approaches for neuromodulation is identified as an area for future development.

Collaboration among researchers in the field of neuromodulation is necessary for further advancements in treatment options.

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The speaker discusses the expansion of symptoms in Parkinson's disease beyond cognitive and memory-related issues.

55:10Collaboration with different groups in computational research is highlighted as driving progress in the field.

The speaker expresses optimism for a product to reach the market by 2025 or 2026.

Appreciation is extended to Dr. Tass and sponsors, along with a call to support upcoming events and donate to help families affected by Parkinson's.

The video ends with expressions of gratitude and farewell messages.

00:00Welcome to our online event the latest

00:03research from Tas lab today's program is

00:06brought to you by Parkinson's Community

00:08Los Angeles today we are so fortunate to

00:11have with us Dr Peter aass

00:16mdphd I'm Angela nef pcla board member

00:20for those of you who don't know us we

00:22are a nonprofit that supports families

00:25living with Parkinson's through free

00:27education programs like this one online

00:31and in-person support groups social

00:34events and more today's conversation is

00:37brought to you by our generous sponsors

00:40Abbot Boston Scientific kioa Kieran

00:45medronic and

00:48suis and by important donations from

00:51people just like you in the Parkinson's

00:53Community if you appreciate our work

00:56please consider making a donation at

01:00your donation is 100% tax deductible so

01:03thank you in advance we rely on your

01:06generosity to help us continue this

01:08important work please join me in

01:11welcoming Dr Tas today Dr Peter Tas

01:16investigates and develops

01:18neuromodulation techniques for

01:20understanding and treating neurologic

01:23conditions such as Parkinson's disease

01:26epilepsy dysfunction following stroke

01:30antonitis he has pioneered a

01:33neuromodulation approach based on

01:35thorough computational modeling that

01:37employs Dynamic

01:39self-organization plasticity and other

01:42neuromodulation principles to produce

01:45sustained effects after stimulation

01:49can't wait to hear about this welcome Dr

01:51Tess thank you very much thanks Angela

01:53for the introduction it's a huge

01:55pleasure to join you this morning and

01:58I'm very grateful for the invitation

02:00so I want to tell you about this this

02:03entire approach and what it is about

02:05it's about basically

02:07stimulating um the brain in a way that

02:10the brain

02:11unlearns the production of abnormal

02:14activity patterns and also changes its

02:17connectivity patterns in a way that we

02:19induce longlasting

02:21sustained relief in Parkinson is

02:26characterized by abnormal neuronal

02:28synchrony synchrony sound sounds nice

02:31intuitively nice because um sounds like

02:33Harmony everybody's doing the same thing

02:35but the problem is if you for example

02:37imagine a company where all employees do

02:39the same things this wouldn't work and

02:40the same with neurons for neurons it's

02:43extremely important that different

02:44neurons that serve different purposes

02:47should be free and able to follow um uh

02:51and and to to um to process the

02:54information they have to process and

02:56therefore synchrony can be really can

02:59really m massively impair brain

03:00functioning if it's too strong and too

03:03longlasting

03:04and since um the activity is close brain

03:09activity in general neuronal activity is

03:11very closely related to synaptic

03:13connectivity meaning the connections

03:16neurons form um pins is also um

03:20characterized by abnormal synaptic

03:22connectivity so as a as a consequence of

03:25the lack of dopamine there a Cascade of

03:28of uh change

03:30of both connectivity and synchrony

03:34you're you're probably familiar with

03:36deep bra stimulation deep bra

03:38stimulation is a was the introduction of

03:41invention of deep bra stimulation and

03:43its introduction to the Parkinson's

03:45field was a huge milestone treatment

03:48Milestone so what you see here is a

03:50Parkinson patient right right-handed and

03:52right sided Parkins and patience 48

03:55years old was no longer to work and he

03:57was one of the patients who really

03:58nicely

04:00um benefited from the treatment so the

04:03electrodes implanted here the the cable

04:07goes to the implantable PS generate and

04:09the important message comes now so the

04:11the ipg the the stimulator has turned

04:14off now and you see the rebound effect

04:18and in general there's no longlasting

04:19effect and this is what attracted me I

04:23first started with medicine I got

04:25intrigued by self-organization processes

04:28wanted to use these S organization

04:30processes in a way to

04:32design um

04:34treatments effective but nevertheless

04:36gentle

04:38treatments and in the the early 90s I

04:41got uh um when I did my PhD in physics I

04:44also studied maths and physics and I did

04:46my PhD in physics in the field of

04:49oscillator Theory

04:51synchronization I was I was really

04:54stunned by the huge effect sies on the

04:56one hand of De brain simulation but also

04:58by the by there slightly weird type of

05:02stimulation pattern stimulus patterns

05:04that were used because they were so

05:06physiological it's a permanent high

05:08frequency type of stimulation high

05:09frequency means more than 100

05:11Herz and in the meantime we understand

05:14very well the limitations of of deep

05:16brain stimulations it's an very

05:19important treatment but it has

05:22limitations on the one hand um since

05:24there are no longlasting therapeutic

05:26effects you typically have to stimulate

05:28for a longer periods of time

05:30and this um this leads to side effects

05:34and in the meantime there's even the

05:36word the term deep bra simulation youth

05:39movement disord so depending on where

05:41the target is where the elect simulation

05:43electrod is locate at different typical

05:45groups of symptoms of side effects

05:48emerge and also deep brain stimulation

05:51is not good in treating all types of

05:54symptoms for example the so-called

05:57actual symptoms do not particularly not

06:00um significantly improve for example

06:03actual symptoms are gate balance and so

06:06on and other symptoms like speech deter

06:09uh Speech or voice impairment may even

06:10get worse um under

06:13DBS so the the approach and this is just

06:16one slide there's been a huge amount of

06:19work and many many many papers so far um

06:22it's very solid stuff it's

06:24mathematically solid biophysically solid

06:28the the the underlying principle is to

06:31counteract abnormal neuronal synchrony

06:34by desynchronizing it so in other words

06:36not surprise supressing it not

06:38inhibiting it but use a um let's say

06:42more gentle type of intervention just

06:45desynchronizing it but this um seemingly

06:49more gentle type of thing is way more

06:51powerful for a couple of reasons and

06:53I'll explain this

06:55now the important point is you even

06:59simple networks and you can show this in

07:01simulations and math mathematical

07:04analysis even simple networks newal

07:07networks with so-called CTIC plasticity

07:11they can be in in a stable different

07:13very different qualitatively different

07:15stable States for example can they can

07:17be strongly connected youve probably

07:19heard of the heum principles NE that

07:21fire together wire together so another

07:23words these neurons are strongly firing

07:25together they have also strong synaptic

07:28connections and here you see it's the

07:31time axis and this is the neuron index

07:33so neuron one up to neuron n n is a

07:36large number you see that all of them

07:38are firing more or less at the same time

07:41so they're strongly connected and strong

07:43synchron and what you can do with

07:45desynchronizing stimulation is you can

07:47desynchronize them so that there's no

07:50coherent structure anymore in their

07:52discharge pattern and and that's the

07:55important point this goes along with a

07:58decrease of the synaptic connectivity

08:00that's very importance and you can think

08:02of it as moving a ball in an attractor

08:07landscape from one pathological

08:09attractor stable state to into the Basin

08:12of Attraction more healthy attractor

08:14state where it remains and this is very

08:17different compared to standard e

08:18stimulation so our goal from the very

08:21beginning is to uce long lasting effects

08:23not to suppress immediately abnormal

08:27rhythms but to stimulate the brain and

08:29the way that bra

08:32unlearns uh its ability to produce

08:34massive abnormal

08:36activity and we've developed a number of

08:40stimulation techniques and are also

08:42currently further improving all them and

08:45optimizing stimulation parameters taking

08:47into account different types of

08:50plasticity mechanisms like synaptic

08:52plasticity structural plasticity where

08:54it's not just whe the sinapsis get

08:58stronger or weak about whether the

09:00entire cups for example

09:02Wes and coordinated reset is a technique

09:06that works in the following way it's

09:08very robust doesn't require difficult

09:11and

09:12sophisticated calibration if you have an

09:17population of neurons for example like

09:19these the SP balls gray balls each ball

09:22representing in urine what you do uh in

09:25the case of standard deep brain

09:27stimulation you position your electrode

09:29in a way that you can stimulate as much

09:32of them because you want to reach them

09:34the mechanism a mechanism of of debrand

09:37simul standard debrand simulation not

09:39yet really fully understood but

09:41basically it might be some sort of

09:43inhibition or blockage and you want to

09:46sort of suppress the

09:48activity what we do is we use for

09:51coordinated reset and this is in way if

09:53we come to the vi tactile later um we we

09:58simulate different subpopulations in a

10:00gentle way the only thing we want to do

10:02is we want to cause a reset meaning a

10:06restart of the rhythmic activity in all

10:09these different subpopulations so for

10:12example if you have if you stimulated

10:13different sites different times and the

10:16neurons are all in synchrony before we

10:18stimulate what happens after such a

10:20coordinated reset Coordinated Time and

10:23Space is that the neurons are no longer

10:27in in Phase their face is mutual phase

10:30difference is shifted if this goes on

10:33for a long period of time what basically

10:35happens is that they reduce their

10:37synaptic weights and so the strength of

10:41their connections and they unlearn their

10:43activity and this is how it looks like

10:45so we do not permanently stimulate but

10:48we have these patterns so it's a mixture

10:51of of periodicity and Randomness so you

10:54see um the period the underlying period

10:57like a clock and and then there's a

10:59random type of sequence Administration

11:03so the sequence is randomized from cycle

11:05to cycle there are off Cycles where we

11:07don't

11:08stimulate providing the urans um with

11:13sufficient time to do physiological

11:15information processing and also and also

11:18exploiting the the the desynchronized U

11:22the desynchronized state that lasts for

11:25a longer period of time and this is how

11:26it looks like in mptp monkeys so monkeys

11:30that are this is 16 fold velocity these

11:33are seconds that's a measurement cage

11:36where the monkeys were in for about um

11:3990 minutes every day and these monkeys

11:42are rendered par conson by mptp but

11:45neurotoxic substance that selectively

11:48destroys uh dopamine production so these

11:51monkeys only have between 5 and 10% of

11:55the docin producing cells left after

11:58this treat Tre men so they are severely

12:00affected as you can see here the monkey

12:01is basically always sitting some of them

12:04really have issues

12:06um um with with food and um the monkeys

12:12were not treated with any

12:15medication and this little hat served to

12:18protect the electrode from being pulled

12:20out because otherwise monkeys were

12:21pulling out the electrode and we

12:24stimulated them only for two hours a day

12:26that's important only two hours a day it

12:27was an external so we stimulate them

12:29from an external stimulator not

12:31implanted because simply because of the

12:33implant implantable generator was way

12:36too large for these little animals and

12:39this is the same

12:40monkey after two hours of coordinated

12:43reset stimulation so to our stimulation

12:46and then brought back into this

12:47measurement cage measurement cage used

12:50the light barrier

12:52system um where where it was that

12:55enabled to to measure the amount of

12:59movement

13:02production and you see that also based

13:05on a quantitive analysis there was no

13:08difference between uh the the monkeys

13:11after two hours of CR stimulation

13:12compared to normal monkeys when it came

13:14to movement production rate and the

13:18important um and the important goes on

13:21like this and let me just and this was

13:23also independently um verified by a

13:26number of other groups and this is just

13:29briefly so these are all these are this

13:32is the amount of this is basically monke

13:35Mobility this is before the five days of

13:39two hours per day treatment so they are

13:42they're not mobile that's the mean value

13:45standard deviation this is during the

13:48days of the five days and this is after

13:51these five days two hour stimulation and

13:53this is with classical DBS standard deep

13:56brain stimulation and there an increase

13:59there a slight after effect that decays

14:02within 30 minutes and this is what we

14:04see with CR with this really low

14:06intensity on purpose low intensity

14:09because we have to stimulate differ our

14:11populations selectively and we have an

14:13significant after effect therapeutic

14:16after effect for one month and this was

14:19important um on the one hand

14:22to move forward with in

14:26patience and we've shown this also in in

14:29externalized patients um where the

14:32electrodes are implanted the the the

14:34cables not yet so the patient was

14:36stimulated I means through an portable

14:39stimulator and this is how it looks

14:43like so this is a 49 years old patient

14:47Parkinson patient she was also a

14:49right-handed person she had

14:52a

14:53um uh dystonia for more than a year at

14:57that time so the patient was able to

14:59stretch her fingers she was instructed

15:01to stretch her fingers but it was

15:03impossible for her to do this this was

15:06now directly before CR

15:10stimulation and you see that fullblown

15:13symptoms Tremor and

15:14dystonia and um we measured the EMG

15:18muscular activity exomer EG and so on

15:23and this is about 20 minutes after

15:25turning on coordinated reset stimulation

15:27you see the symptoms are on and

15:29remarkably also dystonia because

15:31dystonia doesn't respond well when you

15:33use um standard deep brain stimulation

15:36in particular um when you deliver to the

15:39sdn and this was only unilateral

15:42stimulation that's important all our

15:44patients at that time were stimulated

15:45unilaterally for technical reasons and

15:48this is the important thing so this is

15:49now the situation one hour after turning

15:51off stimulation and you see that defect

15:54persists that's the important point and

15:57not only the Clint effect but also so

16:01rigidity was gone and so on but also the

16:04abnormal activity so this is what you

16:06see here so the x-axis is the frequency

16:11axis tells you when when you analyze

16:14signal and in this case the signal um in

16:17the brain it's like a small EG local EG

16:21it's called local field potential

16:23lfp directly at at the site where you

16:27where we stimulated then you can ask

16:30which uh Rhythm which component which

16:33oscillation which Rhythm contributes to

16:35the signal and that's a spectral

16:37analysis the y- axis is spectral energy

16:40and before stimulation you see the one

16:44very prominent Peak around five Herz

16:47that's the Tremor Associated Peak and

16:50this peak that's related to ainan

16:52rigidity and this is after 1 hour after

16:56in total 4 Hour stimulation you see that

16:58that these Peaks are gone and that's

16:59very different compared to standard deep

17:01brain stimulation where this peak

17:04returns within 12 seconds and this one

17:07even

17:08quicker and we've seen this in in all

17:10patients uh I don't want to go through

17:13unnecessary details we' seen this in all

17:15patients and this was very

17:18promising and also the effect size was

17:20very promising but one important point

17:22was the following if we are able to Del

17:26to deliver treatment that has

17:27longlasting effect we have a chance to

17:30do this non-invasively because you can't

17:32wear for example a vibrating glove or

17:35any type of non-invasive device Ty you

17:37typically can't wear it and you don't

17:39want to wear it

17:41247 therefore this longl lasting effect

17:44was um a huge import a huge milestone in

17:48the development of the glove

17:51treatment and there were predictions

17:54also again computat predictions that it

17:57should be possible to do this and this

18:00is simply because the the thing we use

18:02is um we have we it's known since 1980s

18:06of the last uh uh so the 80s of the last

18:09century it's known that we can reset we

18:12can

18:13restart rythmically active neurons I

18:15means all of all sorts of um stimuli not

18:18just electrical stimuli also thermal

18:22stimuli and another stimuli but the

18:24important thing is we can do this by

18:26stimulating the axle we can this by

18:28stimulating sinapsis it's a very

18:31fundamental mechanism we use this

18:33mechanism we don't want to suppress

18:35neurons we just wanted to restart

18:37different un at different times so in

18:39other words we want to manipulate the

18:42timing of different parts of a un

18:45population and there there's a series of

18:48beautiful studies um published by lenses

18:52lab lens is the US neurosurgeon great

18:57neur

18:58surgeon and what they've shown is the

19:02following in order to understand

19:04different parts of the thalamus because

19:08neurosurgeons really want to understand

19:10where they implant their electrodes for

19:12example for the treatment of

19:14corkin they've made the following

19:16observation in a very reliable Manner

19:19and they've done this in Perkinson

19:20patients in ental trauma patients

19:23patients with chronic

19:25stroke and what they've seen in distonia

19:28they've seen is the following if we um

19:32if the electrode is in the in the

19:35central heart for sensory inputs it's

19:38called ventral cordal uh nucleus of the

19:41thalamus so that's basically the heart

19:44that gets all in proceptive information

19:47from the periphery for example from the

19:49hands from

19:52skin then um and we vibrate different

19:56parts of the body can also be the pH

19:58it's a very very general phenomenon need

20:01be just the hands then there are neurons

20:05that do not just um randomly respond so

20:08to speak to the stimulus but they

20:09respond in a rhythmic way and the way

20:12they respond and their rhythms and the

20:16rhythmic responses are tied to the

20:18vibration so if this is the vibration

20:20for example urans VI urans discharge for

20:24example in synchrony with the vibration

20:27and this is shown here so what you see

20:29here is one cycle of the peripheral

20:32vibration of the the skin and the Y AIS

20:36is the

20:37percentage uh is is the number of of

20:39discharges so if there and assume that

20:42there were no uh in no relationships

20:45between the discharges and um the

20:49vibration is just be a noisy flat lines

20:52but what we see is this beautiful

20:54entrainment so what this means is when

20:57we entrain different parts of the brain

21:00can

21:01control the timing of discharges and

21:04that's what we need we don't need to

21:06suppress neuronal firing and we don't

21:09want it because neurons have to be

21:10active in order to learn and unlearn

21:13their connections we really want to

21:15change um these networks and and you

21:20shouldn't think of the brain as a like

21:23as an oldfashioned computer that has

21:25hard wirus um but it's a dynamic system

21:29that permanently changes and also when

21:31I've for example um given my

21:33presentation my goal is to cause a re

21:36wiring on your side and your brains in a

21:38way that you're able to memorize

21:40hopefully memorize what I'm

21:43presenting and now why did we choose the

21:46fingertips and this is because the

21:48fingertips have a huge representation so

21:51what you see here is the humulus there

21:53Al there's also on the Moto side a more

21:55modern version of it but the basic

21:57principle holds as uh as published in

22:01many many years ago by Penfield and that

22:04is the

22:05F not all parts of the body do have the

22:08same cortical representation so the

22:10volume enhance the number of urans in

22:13the cortex in the sensory cortex and

22:15also M cortex that are that are that

22:19process information from the skin of

22:21different parts of the body is very

22:23different it's not homogeneous or so for

22:26example as you can see here

22:28the hand has a huge representation if

22:31you for example compare it with the arm

22:33the arm anatomically is a larger object

22:36larger part of the brain but this Strate

22:39the the the fingertips and the hand are

22:41so strategically favorable simply

22:43because they're a small part of the skin

22:46overall skin but they have such a huge

22:48representation beautifully huge

22:50representation and that's what we want

22:52you want to enter the brain in in a

22:55non-invasive manner in a well defined

22:58Way by means of this phas locking by

23:01means of this entrainment type of

23:03stimulation and we want to um stimulate

23:07a hub part of the brain that is large

23:10large enough we can we can induce a

23:14desynchronizing effect and then as we

23:16know from other preclinical

23:17computational and also clinical studies

23:20desynchronizing effects typically

23:22propagate in the brain so this is the

23:26basic concept uh concept behind it and

23:28so what we've done this this is the

23:30first generation type of glove system we

23:32have vibrators attached to all four

23:35fingers to four fingers not not the

23:37thumb on both

23:38hands and what we do is we simply

23:41replaced vibrations to 150 Herz bursts

23:45by um sorry we we replace the electrical

23:49bursts delivered through depth

23:51electrodes by these vibrations that's

23:54the important thing so instead of

23:56implanting an El

23:58delivering electrical pulse electrical

24:02pulses we simply use vibrate vibrators

24:07well-defined

24:08vibrators and vibrating according to

24:11these well-defined spal temporal

24:15pars we've done a thre Monon pilot study

24:19we've done a number of pilot studies and

24:22this these These are data from a three

24:24months pilot study at that time this was

24:26the co era we wanted to do uh study in

24:3020 patients and follow up patients for

24:33at least two years but you took go we

24:36have to stop hospit was closed and then

24:38fortunately reopened quickly for medical

24:42care surgeries and so on but then later

24:45on we were also able to to restart our

24:48research so it was um therefore it was a

24:52three month pilot study turned out to be

24:54a three-month pilot study all of the

24:56data you've seen here you'll see here

24:59and in the following slide are all um

25:04exams um May done performed after proper

25:08medication withdrawal in order not to

25:11have any interference medication

25:13patients had to withdraw their

25:15medication for between 12 and 48

25:19hours and you see here the amount of

25:21mdss part three scores as I said off

25:25medication scores so the larger the

25:27number

25:28the more um the more impaired the

25:31patient is and the MDS upiter as part

25:33three many of you will be familiar with

25:36this covers all parts of movement

25:38production of the entire body from um

25:42from top to toe and what you see here is

25:45that all of these

25:47patients that's the mean well that's the

25:49Baseline so patients came in that's

25:51acute effects that was the first visard

25:53day was a day visard day um

25:58and deter um focusing on acute effects

26:01meaning effects emerging after two times

26:03two hours stimulation while patients did

26:06not get any medication so patients came

26:09in in the morning at

26:108:00 we did this exam and then we had

26:14two times two hours and in total four

26:16hours glove stimulation in between the

26:20two two times two hours in between a

26:22lunch break and patients didn't get any

26:25medication and then in around 3 3:30

26:27p.m. in the afternoon we did this mdsu

26:32part three this Moto motor exam again

26:34and you see that there a significant

26:36decrease although patients did not get

26:38any medications and some of them are

26:40really afraid of staying off medication

26:42for such a long time they significantly

26:45improved statistically significantly

26:48improved and this is the long-term

26:50effect and this is um most remarkable

26:53and and very encouraging and that is

26:55that's the following so this is patient

26:57then came again for first uh treatment

27:01day

27:02visit and we did the base socalled

27:05Baseline analysis again at 8:00 in the

27:07morning off medication and that's the

27:10mean well and C deviation so to speak

27:15and then after 3 months using the glove

27:18four hours a day or two to four hours a

27:21day patients came in again and at 8:00

27:24in the morning again this medication

27:27will all um this exam mod exam is

27:31repeated and you see this beautiful

27:33Improvement although patients were off

27:37medication and this was super

27:39encouraging of course to change the

27:42brains of the patients change their

27:44conditions on longterm

27:46scale

27:49and now the question is where these

27:51effects only statistically significant

27:53or they also clinically significant and

27:56if you want to talk about Clinic

27:57significance you have to use the

27:59socalled MCI clinically identifiable

28:03difference and the minim clinically

28:05identified gphin is a hurdle in this

28:07case it's minus 3.25 so a decrease of

28:11the motor score greater than 3.25 is

28:14significant and the green data the acute

28:18acute data the acute Improvement on this

28:22very first visit and you see that all

28:24patients at an acute um clinically

28:27significant fute Improvement except for

28:29patient three and cumulative um

28:33improvements after 3 months of of orange

28:36bars and you see that all patients a

28:38clinically significant improve more and

28:42the other thing that's important is that

28:45typically patients had a a reduction of

28:48their medication we did not instruct

28:50patients to reduce their medication

28:53patients um decrease their medication

28:55but of course patients were able to

28:57decrease their medication if needed and

29:01several of them were happy to reduce it

29:03because of side effects that were um

29:06that were bothersome to them so we what

29:09we've seen is a decrease of the

29:12medication and another finding that was

29:15also really surprising to me didn't

29:17expect it to be that pronounced because

29:20it's not so easy to detect Parkinson's

29:23related abnormal Rhythms on the cortex

29:26surface of the

29:28brain um in the depth in depth

29:31electrodes it's it's it's easy and

29:34they're very pronounced and you can see

29:36them by by simply visual by simple

29:39visual exraction but in the cortex it's

29:42it's more ingrate it's more complicated

29:44more sophisticated and what you see here

29:46is these are all patients off medication

29:49again after medication withdrawal before

29:53the treatment and 30 and and sorry 3

29:56months after the treatment with GL

29:58treatment and you see the um these are

30:02the primary motor and primary sensory

30:04cortex so the sensory motor cortex the

30:06primary target for our

30:09treatment and what you see colorcoded is

30:12the power in this High Parkinson's

30:15related very typical high beta B between

30:1821 and 30 Herz so we tested all

30:20frequency bands we didn't find any

30:22significant change compared to Baseline

30:25and three l um glove treatment but this

30:30Parkinson's related beta band had a huge

30:32decrease showed a huge decrease of the

30:36power that was very encouraging because

30:38we didn't expect it to be so

30:41pronounced and so we we did not only see

30:45a clinical substantial Improvement after

30:47medication withdrawals but also from an

30:50electrcal st the N Improvement then we

30:54had a couple of Case Case serious

30:57studies and what you see here is again

31:01the x-axis is St of treatment glove

31:04treatment and the Y AIS is again the

31:06motor score and it was an off medication

31:09again after with medication call off

31:12medication motor score what you would

31:14expect in par

31:16ination um if you think of the time

31:18access here time time rang as here this

31:21is about 9 months is that you would

31:24expect that power concentations get

31:26worse time because of the underlying

31:28condition and

31:31degeneration and the progress of this

31:33degeneration what we've seen here is a

31:36linear decrease in all of these patients

31:39and for example these this patient this

31:41is about half a year and this patient

31:43was stimulated for half a year two to

31:45four hours a day one month pre pause and

31:47then again six month we have um we were

31:52able to follow up due to co

31:53unfortunately only um not in person but

31:56we were following up three patients

31:58remotely that we're going through this

32:01regimen with um 6 month two to four

32:04hours and then one month PR paused and

32:07then in total six month

32:11um a maintenance dose were low dose only

32:14two to three times two hours a week so

32:18not much and all of them had after

32:20effect really lasting after effects for

32:23at least one up to one 1.5 years and

32:26still feeling better better than they

32:28were before so all this is very

32:31encouraging what we of course need is um

32:34very solid testing also against Placebo

32:36effects there are many reasons why we

32:38don't um believe that these are Placebo

32:40effects because Placebo effects

32:42typically are not that systematic the C

32:45effects um vary in time Theo effects

32:49rarely last for very long time and

32:52Tremor does not typically respond to

32:54placeo effects and we have in all our

32:56patients in these patients and all the

32:58other patients the trauma subscores were

33:00always significantly

33:02decreased but nevertheless and I come

33:05back to this later we'll do proper um

33:08control trials also with Placebo meaning

33:11sh so-called sham stimulation groups and

33:15in order to provide you um with I'd like

33:18to provide you with some patient videos

33:20because these are just numbers or dots

33:22and patient Med tell more

33:25comprehensive um

33:27stories and this is one

33:30patient and he was diagnosed in 2007 he

33:35took quite quite some quite a large

33:37number of of um Parkinson's pills was

33:41about 50% in off time every day um often

33:46lying in B often had ly in B because so

33:49stiff used the cane was supposed to use

33:51a wheelchair because it was falling

33:54increasingly often this was July

33:582018 and if

34:01I'm

34:06uh and you unfortunately are familiar

34:09with these

34:10[Music]

34:11um the typical symptoms so there's a

34:15slowness of movement it's difficult for

34:17Po and patients to enter or exit rooms

34:20to change direction turn

34:23around the facial expression M effect

34:27faal expression is decreased arms are

34:29not

34:40swinging and patient came to us in

34:43August

34:442018 and told him there was no

34:47instruction to reduce medication so the

34:50instruction was to use as much

34:52mats um uh as as as required to feel as

34:57as well as possible and this is the

35:00patient after in total two times two

35:02hours a day on the first

35:04evening and you see this pronounced

35:06change you see the Orin smiling again so

35:11their facial expressions there are large

35:13steps the arms are swinging he went down

35:16to from between 20 to 25 to six and

35:20basically this is this was his um his

35:24his level for longer period of time then

35:27and then this was the sixth day of virot

35:30tactile

35:35stimulation he was an

35:39outpatient

35:43uh he came to to the to the outpatient

35:47visits during three consecutive days and

35:49then continued stimulating at

35:52home and he was able

35:55to start re started working and the

35:57interesting thing is that he he was the

35:59first patient who alerted us because he

36:02told us that he was noticed an

36:04improvement of his sense of smell and

36:05taste and um we didn't expect this uh to

36:09be very

36:11open um and therefore we didn't did not

36:14systematically study this we have a

36:16study that will start early next year

36:20where will start we'll study

36:22improvements all all faction and also

36:24Vision because that's something we have

36:27observed um but nevertheless it has to

36:29be systematically studied in um by means

36:32of proper tests and so on but this is

36:34something a couple of our patients

36:36reported there was patients who had

36:38pronounced Al Factory

36:41impairment and then finally fortunately

36:43this was only November 2018 the patient

36:46was able to run his first New York

36:55Marathon

37:03and finally also he he ran Triathlon so

37:07quite amazing

37:08trajectory very happy extremely happy

37:11about this and this is a patient who had

37:15an early uh onset patient was diagnosed

37:18at the age of 25 this is the first day

37:21came to us off Ms prior to viot tactile

37:23treatment and here uh while having sort

37:29of um an athletic type

37:32of um shape patient simply because of

37:36the huge amount of workout he did he had

37:39huge

37:40um issues because of balance issues trem

37:44issues on the right side was scattered

37:46for

37:47DBS um in September 19

37:5219 and this is the the video he sent me

37:55after six weeks of vir Tech uh

38:07stimulation and he didn't need DBS since

38:10then so for quite a while this is

38:13another patient and this this shows you

38:15and that's quite encouraging for us

38:17because um shuffling balance issues

38:20socalled actual ISS actual symptoms are

38:23a huge problem when it comes when it

38:26comes to medication but also in

38:28particular when it comes to De brain

38:30stimulation um and we've seen in in the

38:33patients but this is of course something

38:35you have to verify in in larger cohort

38:38of patients in patient in our pilot

38:41patients what we've seen us that the

38:42effects of the glove treatment are very

38:45favorable so patients will respond to

38:47this um with respect um to to shuffling

38:51so

38:53shuffling

38:55destinations curve in patients want to

38:57for example exit room enter room change

39:02direction change velocity as you see now

39:04for example patient is able to walk in a

39:06more stable way now and then he has to

39:09stop and tries

39:12to get

39:14into normal walking mode and we provoke

39:17it by asking to turn around in a narrow

39:20how way and that's what you see now and

39:23for patient for this patient was really

39:26very difficult to properly

39:32walk even on medication even when he

39:35used his

39:37medication and this is after three

39:39months and that's also I think a nice

39:41illustration why we use these off

39:43medication um exams so why patients have

39:46withraw the medication for between 12

39:49and 48 Hours depending on the half life

39:51of the medication this is we want to see

39:54the patient we want to study the

39:55patient's condition irrespective of um

40:00medication what you see here is that the

40:03patient has greatly improved he told us

40:06that with

40:07medication shuffling was no long no

40:09longer an issue so he was really happy

40:12about it but you still see that the left

40:15arm is swinging right arm is not

40:16properly swinging also the gate is not

40:18really

40:20symmetric and then you see some

40:23shuffling when he turns around and

40:25that's the reason why we do this off

40:26medication type of exams to really see

40:31what's the condition of the patient and

40:34this is now after five

40:40months and this is after six months of

40:43treatment and one month of pre-planned

40:55pause

41:07let me let me finish in um mentioning or

41:10explaining what we've done with we've

41:12invested a huge amount of money and huge

41:15amount of work into further optimizing

41:18it the treatment and in order to come up

41:21with a stimulator with with a glove

41:23system that is able to do what we what

41:25we actually want want to do we have a um

41:28clear study clinical research and

41:31clinical study um strategy we are

41:35currently restarting we start uh start

41:38enrollment for patients in December

41:43January for a couple of pilot studies

41:46and these different types of pilot

41:48studies address different symptoms and

41:50different populations or subpopulations

41:53of patients for example late stage

41:55patients or early stage patients and the

41:59new um the new glove system and all this

42:02is driven computationally and also it's

42:04also relying on very fundamental

42:06physiological mechanisms that we use

42:09will have uh will provides the

42:12possibility to provide further improved

42:15stimulation patterns further and

42:18individualized

42:20stimulation uh stimuli so it's it'll be

42:23calibrated to each single patient each

42:25individual patients will be

42:27personalized the elementary stimulus

42:30that you're going to use and um we'll uh

42:35we will on a on a midterm type of

42:38perspective what we are doing is we'll

42:41also set up we're currently setting up

42:44for these Pilots um we're setting up um

42:48models mathematical models that so to

42:50speak mimic the patients brains like

42:52electronic twins so that we can really

42:54learn how

42:56the elementary stimuli that we deliver

42:59change brain

43:01activity and we measure these um the the

43:05changes and the responses to the simul

43:08both in our simulations and so so to

43:10speak the tronic twins but also in of

43:14course in our patients and all this is

43:16about further optimizing the treatment

43:19and the Cascade of studies is as follows

43:23we first start with a few very well

43:26trying very well elaborate already I I

43:30approved pilot studies not controlled so

43:32with no sham conditions so that we can

43:35nicely interact with patients ask

43:37patients without unblinding them for

43:40example ask them about how it feels how

43:43this difference to life feel and so on

43:46and of course how they feel and then the

43:49next step will be an randomized control

43:51trial is already Irv approved uh which

43:54will also be which will also to start um

43:57next year so second or at latest third

44:02quarter but I think second quarter and

44:04then as soon as we'll get um good

44:07interim results because there are many

44:10things to test for example also

44:12concerning Placebo stimulation groups

44:14sham effects we have to test them

44:17whether we do this properly then they

44:20will'll will'll be able and the

44:22investment is is ready for this to to

44:25come up with the large scale studies to

44:28that aim to provide um to achieve

44:32reimbursement as soon as possible so

44:34this is our goal and I'm super grateful

44:37that I have fantastic lab people who are

44:40really um working in a very dedicated

44:42very enthusiastic way many many good

44:46superb neurologists neurosurgeons um

44:49very strong funding fortunately and um

44:53thank you for your attention thank you

44:55so so much maybe we should start with

44:58this Dr Tess I'm sure you're used to it

45:00everybody wants to know when it's going

45:01to be available what you know what the

45:03timeline is can you you started to go

45:05into the timeline can you very slowly

45:08talk about the timeline that you expect

45:10at this point yeah the the timeline you

45:13see I don't want to make any uh

45:15inadequate promises also and um it's

45:19also it always depends on what what you

45:21want to achieve so to speak and um the

45:25goal here is is something substantial so

45:28fortunately I was was able to team up

45:31with people who are really extremely um

45:35extremely competent in mttech and have

45:39done um mtech approvals and FDA

45:43approvals and in particular

45:45reimbursements for many many times and

45:48the goal here is not just to quickly

45:51achieve FDA approval and and so to speak

45:55have some people make a bit of money but

45:58um do this in the in the most

46:01professional way in order to provide um

46:04reimbursement meaning access to

46:07treatment for as many patients as

46:09possible and as soon as possible and one

46:13thing is um that is very important here

46:16is it there are some unknown things that

46:19are risk factors for example just just

46:21as an

46:22example we want to show and that's

46:25that's important also for reimbursement

46:27but also for for the neurologists to

46:30understand this

46:32treatment um we want to show that the

46:35effects are certainly not Placebo

46:38effects and for this we have to do

46:40Placebo control trials when you have a

46:42sensory treatment you can't like for

46:45example comparing to comparing it to a

46:48pharmaceutical treatment you can't just

46:49take a pill and one pill is the real

46:52treatment contains the substance the

46:54other pill is the placeo it just con

46:56sugar whatever something totally

46:58inactive and um this is not possible in

47:02when you have sensory stimulation you

47:04have to you have to come up with a in

47:07inactive stimulation pattern but

47:10nevertheless the patient has to feel

47:12stimulation and this is important

47:15because patients should not be able to

47:16un blind themselves and we know what we

47:19want to do but we have to test this and

47:21therefore we do not start with an FDA

47:23approval trial but we start with

47:26first um pilot pilot studies also pilot

47:30studies where we test some of the basic

47:33ingredients of this sham

47:35stimulation and the next thing is uh a

47:38controlled proof of concept trial which

47:41hopefully will start in second quarter

47:42of next

47:44year and then and and then as soon as

47:48for example after let's say six months

47:51or something like that an interim

47:52analysis will provide good results an

47:56FDA approval trial that we've already

47:59preparing um should start and then it's

48:03difficult to tell how how fast this will

48:05be because it be very large very

48:07professional professional very large

48:08trial in many many many patients and

48:12there's and certainly not only one side

48:15study

48:16side um and probably also not only in

48:19the US um and this might take a year or

48:24potentially long

48:26so I hope that some like 20 25 20

48:3126ish should be a time at least this is

48:34our goal and we're not delaying anything

48:36it's not that we want to

48:38be unnecessarily slow or whatever over

48:42accurate or whatever we're doing we

48:45working as fast as we can and it's as

48:48professional uh as it I think as it can

48:51get and it's with people that do it in a

48:54very reliable way with a very very goal

48:56and the goal is to provide all patients

48:58with this treatment as soon as

49:00possible

49:02great um interesting question somebody

49:04wants to know when the stimulation is

49:06going on what is the effect and feeling

49:09on the body yeah what what our patients

49:13reported was that it's it's um they it's

49:18a convenient feeling many patients

49:20report a relaxing effect and when we for

49:24example tested the first stimulators the

49:27first glovs in healthy subjects at that

49:30time I was still in Germany before I

49:32moved to Stanford or Institute members

49:35at that time tested the gloves just for

49:37technical reliability and what basically

49:40everybody said was and these were

49:43healthy subjects is that it's that it

49:45had a zentab of effect meaning it was

49:48relaxing didn't make it tired but

49:50relaxing and that's also what the

49:51patients report we'll do a

49:54study where we specifically we will

49:56specifically analyze the relaxing

49:59effects not only psychophysically or not

50:01only psychologically but also by means

50:04of uh EG meaning brain recordings

50:08there's one question sorry s I've seen

50:11can a BBS patient utilize your

50:14device just briefly we um in principle

50:18there's no reason why this should not be

50:20possible so what we what we'll do is we

50:23have uh and what you typically do by the

50:25way is the following when you have such

50:27a question and you have an hypothesis

50:29and the hypothesis our hypothesis yes

50:32should be possible and then we have what

50:34we do is we first do a a pilot study and

50:37that's what we where we already planning

50:39for example we already have approval iob

50:41approval

50:43for postsurgery

50:46Perkinson

50:47patients um that that have no favorable

50:50outcome for example patients that had a

50:52lesioning treatment or a an ultrasound

50:55Sound Treatment have no not um no

50:58sufficient benef didn't have sufficient

51:01benefit from this treatment and in these

51:04patients we will try the glove treatment

51:06and the same we will do with deer

51:09stimulation patients but before I can

51:11make such claim that it actually

51:13benefits patients we have to go through

51:15this usual sequence we first tried in a

51:18pilot study then we go based on the

51:21effect size and the learnings in general

51:23the learnings uh obtained in the pilot

51:26study we go to a control trial with Sham

51:30soal Placebo type of stimulation and

51:32then we can make the claim that it work

51:34someone asked about Parkinson Tremor

51:37have you um do you have a subgroup that

51:40for people who ex excuse me not

51:43Parkinson's Tremor essential

51:45tremor I'm sure you have lots of

51:47different kinds of people who are

51:48participating I believe you said 10,000

51:51people 10,000 people are on the weight

51:53list yeah or on the wait list okay how

51:56many people actually have um for the

52:00next stage that will be

52:03parting so far we about 35 patients um

52:08experience from 35 treating 35 patients

52:12next stage will be um Pilots um about 60

52:18the first three pilots and then um 207

52:24234 in the in the control trial and then

52:28the

52:29larger um FDA approval trial will be a

52:32larger number probably 100 or more so

52:35this is these are the current numbers

52:38and your question concerning essential

52:39tremor we we absolutely want to to test

52:43this treatment also in a essential

52:45trauma patients Parkinson is now highest

52:48priority but essential trauma is

52:50definitely also a goal for us and this

52:53is because um we have we had patients in

52:56our pilot study for example we had a

52:58patient who had a pre-existing essential

53:00tremor and then later on also um

53:04presented with Parkinson symptoms and

53:07the patient had very pronounced trauma

53:10reduction due to the glove both

53:12concerning the ENT typical essential

53:14trauma symptoms but also the Parkinson

53:16trauma symptoms seems like you've had a

53:19lot of accidental good news through your

53:21studies so far yeah fortunately there

53:25were some there were some um some

53:27observations we definitely didn't expect

53:29and we focused of course on the typical

53:31motor effects unfortunately um we had um

53:36quite promising very early and still to

53:39be confirmed in control studies but very

53:42early surprising findings related to

53:45non-motor symptoms here's another

53:47question I'm not quite sure I understand

53:49it but you probably will do most of the

53:52neuromodulation researchers specifically

53:54those who are using the vibratory

53:56approach network with each other as in

53:59the q1 of Charco neurotech I guess it's

54:03just about do you have a large group of

54:05people who are doing similar research as

54:08to you that you um network with no not

54:12yet no not not actually not yet uh I

54:15think this uh this is something that is

54:17about to start and it always takes some

54:19time you see me if you if you look for

54:21example at the at the development of the

54:24deep brain stimul a um research

54:27community and this also took years

54:30initially it was focused on motor

54:31symptoms then it broadened to other

54:34types of symptoms cognitive memory

54:37related symptoms and and also um emotion

54:41emotional lyic symptoms and so on but um

54:45this this will take some time however

54:48concerning the um the underlying

54:51research the computational research

54:53that's driving our field and our

54:56approach I collaborate with several

54:59groups I've I've um PhD students also at

55:02other universities and so on so we are

55:04out of time but the million dooll

55:08question is when when is the updated

55:10timeline for the glove to come to Market

55:13um if all things go continually go to

55:17smoothly is that like two years three

55:19years well my hope is but I can't I I

55:22cannot I don't want to overstate or over

55:25promise or whatever and there are some

55:26things that you cannot can never can

55:29never um predict uh adequately but what

55:34I hope is that 2025

55:372026 okay I think that's a realistic

55:40number I that's I know that was a tough

55:42question to ask but everybody wanted to

55:43know the answer so I had to ask it so

55:46thank you again Dr Tass and thank you

55:48for all for joining us today today's

55:51event was made possible by our sponsors

55:53Abbot Boston scientist ific kioa Kiran

55:56medronic and suis we have some wonderful

56:00events coming up which I'll tell you

56:02about in a moment but if you enjoyed

56:04today's program please visit

56:11pcl.is to improve the lives of families

56:13in our community living with Parkinson's

56:16you can find our contact information at

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56:23deductible thank you every everyone and

56:25have a wonderful wonderful day byebye

56:29thank you very much for the invitation

56:31thank you Dr

56:36Tas

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