WO2019171091A1

WO2019171091A1 - Method for transferring molecular information of a drug substance to living tissues

Info

Publication number: WO2019171091A1
Application number: PCT/HU2019/000005
Authority: WO
Inventors: Gyözö VASZILJEVICS; Tibor VELLAI
Original assignee: Vasziljevics Gyoezoe; Vellai Tibor
Priority date: 2018-03-09
Filing date: 2019-03-04
Publication date: 2019-09-12
Also published as: HUP1800087A1

Abstract

The present invention relates to a method for non-invasive transfer of molecular information of a drug molecule into living tissues. More particularly, the present invention relates to a pharmaceutical method which, without the direct administration of the drug substance, is merely done by recording the molecular information of the drug substance and then delivering it non-invasively to the living tissues in a suitable manner. The invention may be particularly suitable for treating conditions in which the delivery of the drug substance to the target area by conventional methods does not lead to satisfactory results, or the toxicity of the drug may be a significant risk factor during the therapy.

Description

Method for transferring molecular information of drug substance to living tissues

The present invention relates to a method for non-invasive transfer of molecular information of a drug molecule into living tissues.

More particularly, the present invention relates to a pharmaceutical method which, without the direct administration of the drug substance, is merely done by recording the molecular information of the drug substance and then delivering it non-invasively to the living tissues in a suitable manner.

The invention is particularly suitable for treating conditions in which the delivery of the drug substance to the target area does not produce satisfactory results by conventional methods, or the toxicity of the drug may be a significant risk factor during the therapy.

Such conditions include, but are not limited to certain forms of cancer therapy, age-related and other pathological conditions that are difficult or unmanageable to treat. For example, in the case of neurodegenerative diseases, drug candidates operating effectively in cell culture often fail when they are introduced into living organisms because the drug molecules are unable to pass through the blood-brain barrier, which evolved into a natural filter system that inhibits the entry of harmful substances and pathogens into the central nervous system.

One of the most prominent areas of the former is the treatment of age-related pathological conditions.

The aging process is caused by the ever-increasing accumulation of cellular damage throughout life. The accumulation of these molecular damages also leads to age-related diseases (various types of tumor diseases, neurodegenerative lesions [Alzheimer, Parkinson's and Huntington's disease], diabetes, tissue atrophy [especially sarcopenia], fibrosis, immunodeficiency states and infections by intracellular pathogens) (Kirkwood, 2008). Such cellular damage includes, for example, defectively folded or non-folded (misconfigured), oxidized and aggregated proteins, which, beyond being unable to adequately perform their biological function, act as a cellular poison to disrupt normal cellular function processes. Effective removal of cellular damages therefore is essential for stable maintenance of cellular homeostasis and cellular function. When the removal of cellular damage is disrupted, the affected cell can initiate its own self-destruction program (apoptosis) to maintain the integrity of the affected tissue by removing the damaged cells. This massive cell death manifests itself in diseases of the elderly and ultimately leads to the death of the living being. Since the molecular background of aging and age-related diseases is the same (accumulation of molecular defects), it is not surprising that these diseases occur more often in older age and not in young people (Sturm et al., 2015, 2017).

One of the most significant and most common types of degenerative lesions in the elderly is neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), or Huntington's disease (HD). These diseases are not yet curable deadly pathologies that affect a relatively large proportion of the elderly human population of the 'developed world'. In the United States, for example, every third elderly person has been affected by AD and the treatment of patients is a huge economic burden on society. People with AD can survive for decades after the onset of symptoms and need help from healthy people in their daily activities.

The accumulation of non-functional, abnormal proteins (proteotoxicity) leads to the development of neurodegenerative diseases (Rubinsztein, 2006). Such diseases are commonly referred to as proteinopathies. AD is caused by intracellular accumulation of extracellular beta-amyloid or hyperphosphorylated Tau proteins, whereas intracellular accumulation of mutant alpha-synuclein or Parkin proteins leads to Parkinson's disease, whereas Huntington disease is the result of intracellular accumulation of mutant Huntington protein. In these neurodegenerative diseases, accumulation of damaged proteins is characteristic of certain brain regions.

In healthy cells, defective proteins are effectively removed by cellular degradation processes: autophagy and the ubiquitin proteasome system (Levine and Kroemer, 2008). The most significant form of cellular degradation is autophagy (lysosome-mediated cellular self- digestion). During autophagy, some parts of the cytoplasm (macromolecules and cellular organs) enter the lysosomes, where they are enzymatically degraded. This process begins with the formation of a double membrane structure (phagophore or isolation membrane) that surrounds the materials designated for degradation. During the membrane formation, a vesicle is formed, which is called an autophagosome. The autophagosome then fused with the lysosome, creating the autolysosome, which is an acidic cellular constituent. Within it, degradation occurs by acid hydrolases (proteases, lipases, nucleases and glycosylases). An autophagy disorder may accelerate aging and lead to the early appearance of various neurodegenerative lesions (Vellai, 2008).

Autophagy plays a central role in maintaining the function and integrity of the nervous system, and this process has become a promising target for drug development in the last decade. Several autophagy enhancers have been developed. Most of these drugs exert their effects through a target protein remote from autophagy, so their use often leads to unwanted side effects. Such an autophagy stimulating agent is, for example, rapamycin, which specifically inhibits the cell energy sensor kinase, TOR (target of rapamycin), which is the major negative regulator (inhibitor) of autophagy. Rapamycin is capable of inducing autophagy in both cell lines and in vivo models. In addition to inhibiting autophagy, TOR regulates many other processes in the cell, including translation and ribosome formation. Thus, the use of rapamycin can interfere with a number of other important cellular processes leading to unwanted side effects during therapy.

In recent years, many small molecules have been identified based on their ability to induce autophagy by inhibiting MTMRl4/Jumpy (Papp et al., 2016; Billes et al., 2016; Kovacs et al., 2017). MTMRl4/Jumpy is an antagonist of Ptdlns-3K kinase. Ptdlns-3K kinase converts Ptdlns to Ptdlns-3P, which is indispensable for autophagous membrane formation. Drug candidates that inhibit MTMRl4/Jumpy-t have a prolonged lifespan and neuroprotective effect.

Such low molecular weight agents are also known from, for example, International Patent Application WO 2015/079067.

One of the promising drug candidates is AUTEN-67 (autophagy enhancer 67), a compound of the following formula:

under the chemical name N-(3-(l H-benzo[d]imidazol-l -yl)-J4-dioxo-J4-dihydronaphthalen- -2-yl)-4-nitrobenzenesulfonamide. It is verified that this small molecule is capable of enhancing autophagy flux in various mammalian cell lines, as well as in Drosophila melanogaster, Zebrafishes and mice (Papp et al., 2016; Billes et al., 2016; Kovacs et al., 2017). AUTEN-67 also has a significant anti-aging effect: the drug significantly increases the life of Drosophila. The molecule effectively inhibits the accumulation of toxic mutant proteins and the destruction of certain neuronal groups in Drosophila PD and HD models (Kovacs et al., 2017; Billes et al., 2016). In addition, it improves the ability of animals to climb in the same disease models. AUTEN-67 protects human cells and mouse isolated neurons (primary cell culture) from treatment-induced oxidative stress and improves nesting behavior of AD model mice (Papp et al., 2015).

Although AUTEN-67 is a small molecule, it is unable to cross the blood-brain barrier. It is well known that the blood-brain barrier is a natural barrier between the central nervous system and the blood stream, which prevents the introduction of toxins or pathogens present in the blood into the central nervous system. Therefore, agents that pass through the end-brain barrier or procedures that evade this barrier would be required to treat central nervous system disorders.

To date, however, there is no known molecule that effectively crosses the blood-brain barrier and protects neurons from destruction by molecular stress.

Our goal was to find a solution to the problem outlined above.

In our experiments, we have discovered that some types of millimeter wavelength (MW) therapeutic devices may be suitable for solving the problem raised.

The biomedical effects of millimeter waves were discovered at the end of the l960s and were widely used in the former Soviet Union since the l970s.

The principle of the method known as "MM wave therapy" (Low Intensity Millimeter Wave Therapy) or "EHF Therapy" (Extreme High Frequency Millimeter Therapy) was developed by Gyevjatkov et al. (1991). As a result of their work, equipment has been developed worldwide. These operated in the frequency range of 30-60 GHz, i.e. in the wavelength range of 5 to 10 mm, either on a discrete constant frequency or on a "noise"-like radiation consisting of a mixture of frequencies within the range. The energy of the used radiation is low (10-30 W/cm²) and the treated surface is typically 10 cm². Equipment for the treatment and its application can be found in, among others, the following patents and patent applications:

SU 1611345 A 1 (1990), RU 2082459 Cl (1997), RU 2127616 Cl (1999), RU 2127616 Cl (1999), US 2016/000504 Al (2016), EE 05541 Bl (2011), EE 201000017 A (2010), EE 201000048 A (2010).

Some of the devices described in the documents are commercially available. Examples include the LENYO family (Hippocampus BRT Kft.) And the TRIOMED family (Cemmedic Europe Kft.)

In the study of the devices, it has been found that some devices interact with the tissues of the treated subject not only at the device-dependent and preset resonant frequencies, but also they are also capable of extracting and storing information on vibrations associated with cellular function in an organism; and then suitably radiating it back. In this manner e.g. the device can be used in the treatment of certain diseases through the transmission of information of a healthy organ function.

MW Therapy has been used for over 30 years on a wide range of disease treatments. Diseases that are treated with MW therapy include: certain gastrointestinal disorders (peptic ulcer, gastroduodenitis), diabetes mellitus; coronary artery disease and some other circulatory disorders, cerebral palsy, chronic non-specific lung diseases, skin diseases such as psoriasis and atopic dermatitis, bone and wound healing, treatment of certain cancer types and immunodeficiency states, and alleviation of side effects of chemotherapy and radiotherapy. The MW treatment has also produced promising results for those with opioid, alcohol and nicotine addiction (Ziskin et al., 1998).

However, no data were found suggesting that such devices would have been used to transmit information on non-organic substances, such as simple compounds, especially drug substances, or even investigated the possibility of such methods.

However, we assumed that if the MW device succeeds in transferring the molecular information of a drug substance to an organic organism, it could solve the problem outlined and would allow a non-invasive procedure to treat pathological conditions in which direct drug therapy could not produce satisfactory results (e.g. by passing the blood-brain barrier and introducing drug substance directly into the central nervous system). Experiments have been carried out to prove our assumption and our results prove that using the method developed on the basis of our recognition, molecular information of an active substance - in this case AUTEN-67 - and thus its neuroprotective effect, can be introduced into living tissues, including the brain.

By this method, the pharmacological effect of other small molecules— Neuroprotective or other low weight molecules that cannot pass through the blood-brain barrier (drugs) - can be introduced into the brain.

However, our experiments do not limit the scope of the active ingredients to the active ingredient herein, which is intended to show only the demonstration of our invention and its results, implying that our results can be applied, mutatis mutandis, to other similar small molecules to achieve the desired effect, which are also contemplated by the present invention.

For our experiments we used the commercially available TRIOMED MMW, which is marketed by CEMMED.

(Contact: www.cemmed.ru, www.cemmed.hu or www.cemmedeurope.com)

According to the application description of TRIOMED MMW, it is suitable for recording the wave state of a living organism and stored in its special transducer for later therapeutic radiation.

Surprisingly, it has been found in our experiments that the apparatus is also capable of capturing and recording the vibration state (molecular information) of any molecule, and is able to introduce this fixed information into living tissue later.

Thus, the device is capable of transferring molecular information (vibration state) from one location (e.g. from an active ingredient stored in a glass vial) to another site (e.g. into living tissue).

Thus, for example, it is suitable to introduce spatial information of molecules and its resulting effect that cannot pass through the blood-brain barrier into the central nervous system in a non-invasive manner. Our invention is illustrated by the following examples:

Example 1

A.) As a reference, it is shown that the administration of AUTEN-67 small molecule by "oral" feeding increases the amount of autophagic structures in the fat body cells of the larval body of Drosophila.

The Drosophila homozygous V9 animals used in the experiment, i.e., y, w, hsFlp; UAS-DCR- 2; pAct <CD2 <Gal4, UAS-nlsGFP, r4-mCherry-Atg8a is a genotype whose intracellular flow of autophagy in fat body cells can be traced by microscopic examination of cell samples based on the number of red spots appearing in the field of vision of the epifluorescence microscope.

Both the sustenance and the genetic work and cross-breeding of the Drosophila strains were carried out in an environment of 18 °C to 25 °C. For the sustenance, one of the traditional media containing agar-comflour-sugar-yeast was used as a nutrient for our work: The composition and preparation of media is as follows:

For cooking 1 liter of medium, 66.85 g of com flour, 32.59 g of sugar, 10 g of agar and 26 g of yeast were used.

After weighing, 1 liter of cold water is added, mixed well, and cooked in a microwave oven for 17-20 minutes (800W), stirring at every one and a half to two minutes to become knotless.

The final medium was allowed to cool for 20 minutes and then (at about 60 °C) a solution of 10 ml of 25% (w/v) nipagine (4-hydroxymethylbenzoate) in 96% ethanol was added. Subsequently, about 4-7 ml culture medium per tube was added to the glass vials.

During the reference experiment data of the following samples were compared:

- A Fat body cells of untreated, normally held (well-fed) animals,

- A’ Fat body cells of normally held (well-fed) animals treated with AUTEN-67,

- B Fat body cells of untreated starved animals,

- B’ Fat body cells of starved animals treated with AUTEN-67,

- C Fat body cells of untreated animals

- C’ Fat body cells of an animal treated with AUTEN-67. The 76-89 hour-old animals used in the experiment were fed with the following nutrient-rich medium:

0.825 g com flour

0.405 g sugar

0.585 g yeast

+ 2 ml water

Preparation: cooked in a small Petri dish with a lid on in a microwave oven 3 times for approximately 3 to 5 seconds until dry state, then add 1-2 ml of water to ensure proper consistency.

"Starved" animals did not receive nutrients in the 24 hours prior to the experiment.

The nutrition of AUTEN-67-treated animals also contained 10 or 100 gg of active substance dissolved in DMSO, while the feed material for untreated animals was DMSO alone.

The fat bodies of the animals were dissected in PBS, and a glycerin-PBS solution containing Hoechst nucleus dye was applied to the embedded lobes to make the sample transparent and display the nuclei. Recordings were made using a Zeiss Axiolmager Zl epifluorescent microscope with an eye-focal attachment. For quantitative evaluations, AxioVision 4.82 and ImageJ 1.45s were used, while for statistical analysis, MATLAB 7.12.0 was used.

The experimental results are summarized in Figures 1 and 2.

Figure 1 shows microscopic images A to C’, which have the same designations as those listed above, and red dot-like objects refer to autophagic structures (autophagosomes and autolysosomes). The estimated results of these are quantified by column diagrams in Figure 2.

It can be seen that the fat body cells in the treated animals of AUTEN-67 contain significantly more structures referring to autophagy.

B.) The example further illustrates that the non-invasive delivery of information from AUTEN-67 to Drosophila larvae also increases the number of autophagic structures in fat body cells.

Similarly, Drosophila homozygous V9 animals, i.e., y, w, hsFlp; UAS-DCR-2; pAct <CD2 <Gal4, UAS-nlsGFP, r4-mCherry-Atg8a were used, a genotype, in which the intracellular flow of autophagy in the fat body cells can be traced by microscopic examination of cell samples based on the amount of red spots in the field of vision of the epifluorescence microscope. During the implementation of the test, the difference to the above reference example was that no active ingredients were present in the nutrients during the feeding of the larvae; only the TRIOMED MMW device preprogrammed "Information encoder 111 " was used on each active substance and reference material in a non-invasive manner.

The recording and storing of the molecular information of AUTEN-67 and other "reference materials" (air, yeast extract and rapamycin) was done according to the instruction manual of the TRIOMED device, using the special "Information encoder 111 ", which is available for the device. The recording time was optimized by the device, which was 30 - 60 seconds. During the recording phase, the "Information encoder 111 " connected to the device was attached to the wall of the glass vessel containing the active ingredient.

During the experiment data of the following samples were compared:

- A Fat body cells of the untreated (control) animals,

- A’ Fat body cells of animals treated non-invasively with the information of "AUTEN-67",

- B Fat body cells of animals treated with "air information" (negative control)

- B' Fat body cells of animals treated with“yeast extract information” (negative control),

- C Fat body cells of animals treated with "information" of known autophagy inducing rapamycin (positive control),

- D Fat body cells of animals treated with "AUTEN-67 information"

The duration of the transmission of information (i.e. "treatment") was 3 hours, which is equal to 3 hours of feeding. During the execution, 20-25 animals were placed in a small, covered Petri dish and the transducer storing the information was placed at the top of the Petri dish fitting to its center. The period for the control animals was the same, but no treatment based on information transfer was applied. During the experiment, sample B and B' (air and yeast) were used as controls, while rapamycin information was a known positive control.

A controlled experiment was performed as described above to investigate whether treatment with AUTEN-67 information was sufficient to induce autophage activity in fat body cells. First, well-fed animals were treated with the information of air or yeast suspension (feed source for animals) as two independent negative controls. The amount of autophagic structures did not increase as a result of these treatments, but remained at the level of untreated control samples. Subsequently, as positive control animals were treated with rapamycin information - rapamycin is a well-known molecular activator for autophagy. This treatment significantly increased the number of autophagic structures compared to control animals. Finally, the animals were treated with the information of AUTEN-67, which significantly increased the number of autophagic structures. This change in autophage activity was comparable to that caused by treatment with rapamycin information. Thus, our method is suitable for introducing molecular information into living tissue (e.g., nerve tissue).

The results are summarized in Figures 3 and 4.

Figure 3 shows the red dot-like objects on autophagic structures (autophagosomes and autolysosomes) on microscopic images A - A’, which have the same designations as those listed above. The result is quantified by the bar graph A” below the microscopic capture. In the case of the "information-treated" sample, the fat body cells of treated animals contain significantly higher number of autophagic structures, and its extent is comparable to that of the active ingredient introduced by direct feeding (see Figure 2).

In figure 4, the microscopic images of sample B - B’, C and D and the data quantified on the E bar graph under the images can be used to quantify the autophagic structures in the fat body cells of the animals treated with different molecular "information" as the average number of structures per cell. (The mean ± standard deviation values are shown in the diagram, *: P <0.5, independent t-test with Bonferroni correction).

As can be seen, fat body cells from AUTEN-67 treated animals (A¹ and D captures), as well as animals treated with rapamycin information (C capture), contain significantly higher number of autophagic structures, as opposed to untreated sample A, B and B' (air and yeast extract) captures as negative control.

By comparing the experimental data with the data of the reference example, it can also be stated that in the samples treated with the information of AUTEN-67 (Figures 4 A and D), the number of autophagic structures can be found in substantially the same amount as in the reference example (administering AUTEN-67 by direct feeding) as shown in the recordings of A'-B '-C in Fig. 1.

All this proves that the introduction of the information of the active ingredient causes the same effect as that of the active ingredient (i.e., "taking in"). It is important to emphasize that these animals did not eat AUTEN-67 but were treated with its molecular information. This information treatment was able to induce autophagy in living tissues, including fat body.

Example 2

This example demonstrates the motility of untreated (control), AUTEN-67-treated and AUTEN-67-treated expressing human mutant HTT animals and their comparison with the mobility of "normal" animals without this mutation.

A.) As a reference, in the classical "long-term" climbing ability test, we first compared the motor functions of the progeny of W" ¹⁸ ; UAS-128Q-HTT x Appl-Gal4, y, w * crosses (Drosophila expressing human mutant HTT) to the motor function of the progeny of W¹¹¹⁸; UAS-16Q-HTT x Appl-Gal4, y, w * crosses (Drosophila expressing the non-mutated normal human HTT) by direct (fed) treatment with AUTEN-67.

The strains were obtained from the Bloomington Drosophila Stock Center (Indiana University, Bloomington, US, Indiana). Their maintenance was performed on a conventional agar-comflour-sugar-yeast containing medium as described in Example 1. Following the hatching from the eggs, the animals were kept at 29 °C and placed in a new tube every two days. In the experiments, animals of 14 days of age were used.

During the last transfer prior to the experiment, 65 mΐ of the solution of AUTEN-67 dissolved in DMSO (Sigma, D8418) was added to the medium for the treated samples, while the same volume of DMSO was added to the control samples without AUTEN-67.

The results of the following samples were compared in the experiment:

- A UAS-16Q HTT Drosophila Control without treatment

- B UAS-16Q HTT Drosophila, treated with AUTEN-67 (feeding)

- C UAS-128Q-HTT Drosophila control without treatment

- D UAS-128Q-HTT Drosophila, treated with AUTEN-67 (feeding) On the day of the study, 20-20 females were randomly selected from the tubes containing the animals and the test was performed on these specimens. After carbon dioxide anesthesia, the animals were placed in a thin, specially made glass tube (length 25 cm; diameter 1.5 cm) then the tube was plugged with cotton wool. After the anesthesia, we waited for two hours and then started the measurement. Holding the bottom of the glass containing the animals vertically, the tube was gently knocked downwards five times, ensuring all the animals were dropped to the bottom of the tube. For this effect, the animals respond with negative geotaxis and begin to climb up the wall of the glass tube (the space constraint in the tube does not favor the flight). The execution of the experiment is shown in the photograph of Figure 5.

Observing the animals, it was recorded how many animals reached the top of the tube in 20, 40 and 60 seconds (how many animals reached the line at 21.8 cm). In each case, we worked with 3 replicates and repeated the experiments three times (inserting 20-minute breaks).

The results of the experiments are shown in the bar graph of Figure 6, where it can be seen the extent of reaching the target by animals in each sample after 40 and 60 seconds. It can be seen, the ability of animals to move in the absence of Huntington's disease (16Q HTT) is good and independent of whether they received AUTEN-67 or not. In contrast, in mutant Huntington's disease-expressing animals (128Q HTT), reduced mobility of control animals was significantly improved by treatment with AUTEN-67 and substantially equivalent to "normal" animals.

B.) In the continuation of the experiment, we demonstrate how the non-invasive treatment with AUTEN-67 influences motor function of the progeny of W^{I ! I8}; UAS-128Q-HTT x Appl- Gal4, y, w * crosses (Drosophila expressing human mutant HTT).

The experiment was performed as described in the reference section, except that none of the animals were fed with AUTEN-67 in the nutrients, and the control animals were treated with laboratory air information as follows:

- C 'UAS-128Q-HTT Drosophila Control, treated with the Information of Laboratory Air

- D 'UAS-128Q-HTT Drosophila treated with the information of AUTEN-67

Transmission of AUTEN-67 Active Substance and Reference Material (Laboratory Air) information was only done by non-invasive application of the preprogrammed“ Information encoder 11G of the TRIOMED MMW. The recording and storing of the molecular information of AUTEN-67 and the laboratory air was carried out in accordance with the instruction manual of the TRIOMED device, with the special “ Information encoder 111” available for the device. The recording time was optimized by the device, which was 30 - 60 seconds. During the recording phase, the “ Information encoder 111” connected to the device was attached to the wall of the glass containing the active ingredient. When storing the information of the laboratory air the encoder was at a distance of one and a half meters from any other object suspended on the transmitter's USB connector.

The adult Animals received information treatments (air in the corridor of the department, AUTEN-67) throughout the l4-day sustenance cycle. 33-35 females and 7 males were in the breeding tubes.

The climbing ability test was performed as described in the reference as follows:

On the day of the study, 20-20 females were randomly selected from the tubes containing the animals and the test was performed on these. After carbon dioxide anesthesia, the animals were placed in a thin, specially made glass tube (length 25 cm; diameter 1.5 cm) then the tube was plugged with cotton wool. After the anesthesia, we waited for two hours and then started the measurement. Holding the bottom of the glass containing the animals vertically, the tube was gently knocked downwards five times, ensuring all the animals were dropped to the bottom of the tube. For this effect, the animals respond with negative geotaxis and begin to climb up the wall of the glass tube (the space constraint in the tube does not favor the flight). Observing the animals, it was recorded how many animals reached the top of the tube in 20, 40 and 60 seconds (how many animals reached the line at 21.8 cm). In each case, we worked with 3 replicates and repeated the experiments three times (inserting 20-minute breaks).

The results of the experiments are quantified by the bar graph shown in Figure 7, showing the percentage of the experimental animals reached the target within 40 and 60 seconds. The results verified that the AUTEN-67 information showed a significant improvement in the mobility of non-invasively treated mutant animals compared to control (air information) animals, and that this improvement was comparable to that of Figure 6, sample D', i.e., in the case of a sample fed with the active ingredient.

Therefore our method is suitable for introducing molecular information into living tissues. Cited literature:

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Claims

1. Method for non-invasively transferring molecular information of drug substance molecule to living tissues, characterized by that the molecular information of said drug substance is read out with a millimeter wavelength therapeutic device and stored in the device or in its encoder or transmitter, and if desired the stored information is transmitted into living tissues.

2. The method according to claim 1, wherein the drug substance molecule is an agent for treating neurological damage.

3. The method according to claim 1 or 2, characterized by that the drug substance molecule is an agent for the treatment of Alzheimer's disease (AD), Parkinson's disease (PD) or Huntington’s disease (HD).

4. The method according to any of Claims 1 to 3, characterized by that the drug substance molecule is N-(3-(lH-benzo[d]imidazol-l-yl)-l,4-dioxo-l,4- dihydronaphthalen-2-yl) - 4-nitrobenzenesulfonamide or a physiologically acceptable salt thereof.

5. Use of a millimeter wavelength therapeutic device suitable for recording molecular information of an organic tissue to record the molecular information of a non- biological material sample and, if desired, to transmit the recorded information.

6. Use according to claim 5, wherein the non-biological material is the drug substance.

7. Use according to claim 5 or 6, wherein the drug substance is an agent for treating neurological damage.

8. Use according to any of claims 5 to 7, wherein the drug substance is an agent for treating Alzheimer's disease (AD), Parkinson's disease (PD), or Huntington's disease (HD).

9. Use according to any of claims 5 to 8, wherein the drug substance is N-(3-(lH-benzo[d]imidazol-l -yl)-l ,4-dioxo-l ,4-dihydronaphthalen-2-yl)-4- -nitrobenzenesulfonamide or a physiologically acceptable salt thereof.