WO2021053339A1

WO2021053339A1 - Device for destroying extended beta-amyloid

Info

Publication number: WO2021053339A1
Application number: PCT/GB2020/052256
Authority: WO
Inventors: David Andrew Walker
Original assignee: Dglp Ltd
Priority date: 2019-09-19
Filing date: 2020-09-17
Publication date: 2021-03-25
Also published as: GB2587222A; GB201913523D0

Abstract

Alzheimer's disease is characterized microscopically by the combined presence of 2 classes of abnormal structures: extracellular amyloid plaques and intraneuronal neurofibrillary tangles, both of which comprise highly insoluble, densely packed filaments. The soluble building blocks of these structures are Beta-Amyloid peptides for plaques and tau for tangles. The present invention uses transducers to emit an electromagnetic pulse into the forearm of the patient to identify and destroy extended Beta-Amyloid protein within the blood stream.

Description

DEVICE FOR DESTROYING EXTENDED BETA-AMYLOID

The present invention relates generally to a device for destroying extended Beta-Amyloid protein within the blood of a patient and finds particular, although not exclusive, utility in the treatment of Alzheimer’s disease (AD).

Pulsed electromagnetic field therapy (PEMFT) has been used successfully in the management of postsurgical pain and edema, the treatment of chronic wounds, and in facilitating vasodilatation and angiogenesis. Conventional PEMFT enables modulation of Calcium (Ca2+) binding to Calmodulin (CaM), upon a transient increase in intracellular Calcium when homeostasis is interrupted. Disruption of the tightly regulated Ca2+ balance in cells is the natural signal to provoke the endogenous tissue repair and regeneration mechanism, hence the apparent simple acceleration of normal healing activity by targeted PEMF signals. Ca/CaM catalyzes Endothelial Nitric Oxide Synthase (eNOS), which allows the PEMF signal to modulate the release of Nitric Oxide (NO) from eNOS and potentially affect the entire tissue repair pathway, from pain and edema to angiogenesis, bone and tissue regeneration, and other regenerative actions. Because of the unique biologic mechanism of the PEMF effect, this modality can be combined quite effectively with other therapies for additive or supra-additive effects to promote pain relief, healing, and recovery.

The present application identifies an entirely new application of PEMFT, and a new apparatus permitting fine control of the pulsed electromagnetic field.

Alzheimer’s disease is characterized microscopically by the combined presence of 2 classes of abnormal structures: extracellular amyloid plaques and intraneuronal neurofibrillary tangles, both of which comprise highly insoluble, densely packed filaments. The soluble building blocks of these structures are Beta-Amyloid peptides for plaques and Tau for tangles. Beta-Amyloid peptides are proteolytic fragments of the transmembrane amyloid precursor protein, whereas Tau is a brain-specific, axon-enriched microtubule-associated protein. When such deposits form in the brain, neurodegenerative processes are triggered that lead to loss of memory and cognitive ability.

There are five types of leukocyte or white blood cell, each of which reacts to a specific chemical stimulus. The present invention seeks to mimic that stimulus, triggering the white blood cells to destroy the extended Beta-Amyloid protein.

According to a first aspect of the present invention, there is provided a device for destroying extended Beta-Amyloid protein within the blood of a patient, the device comprising: a strap for attachment to a forearm of the patient; a housing attached to the strap; at least one transducer configured to transmit a pulse into the forearm of the patient; a control unit configured to: operate the at least one transducer to emit a pulse; receive a signal from the at least one transducer indicative of a reflection of the pulse from extended Beta-Amyloid protein within the blood of the patient; and in response to receiving the signal, operate the at least one transducer to emit electromagnetic modulations that trigger white blood cells to destroy the extended Beta-Amyloid protein within the blood of the patient; and a power supply for supplying electrical energy to the control unit.

The forearm may comprise an inner forearm, and or a location approximately three finger-widths from the wrist of the patient, for example the location for determining the radial pulse of the patient and/or called Pericardiam6, Nei Guan (P6 or PC6) in the field of acupuncture.

Beta-Amyloid is best known as the misfolded peptide that is involved in the pathogenesis of Alzheimer's disease, and it is currently the primary therapeutic target in attempts to arrest the course of this disease. This notoriety has overshadowed evidence that Beta-Amyloid serves several important physiological functions. Beta-Amyloid is present throughout the lifespan, it has been found in all vertebrates examined thus far, and its molecular sequence shows a high degree of conservation. These features are typical of a factor that contributes significantly to biological fitness, and this suggestion has been supported by evidence of functions that are beneficial for the brain. The putative roles of Beta-Amyloid include protecting the body from infections, repairing leaks in the blood-brain barrier, promoting recovery from injury, and regulating synaptic function. Evidence for these beneficial roles comes from in vitro and in vivo studies, which have shown that the cellular production of Beta-Amyloid rapidly increases in response to a physiological challenge and often diminishes upon recovery.

The Inventor has proven that in an Alzheimer’s sufferer a chemical attraction occurs in the viscous flow whereby tissue that has broken off the arterial wall, attaches to a normal Beta-Amyloid protein. This combination attracts a Tau attachment and peptide fragments to the original Beta-Amyloid protein; referred to in this document as ‘extended Beta-Amyloid protein’ or ‘extended protein’.

This extended protein has a number of characteristics that both contribute to Alzheimer’s disease, and make it readily identifiable. The extended protein now differs from the normal Beta-Amyloid protein in that, it has increased in size and formation (as a result of the attached items) and is also ‘sticky’ due to the Peptide fragments.

In an Alzheimer's patient, the extended proteins accumulate to form plaques that block the synapses, the space between two nerve cells which transmit information, in the brain. This has the result of impairing memory and cognitive functions in the sufferer and ultimately causing death.

The invention uses calculated electromagnetic pulses, to identify a specific entity of known makeup and characteristics (i.e. the extended protein). The signature of the extended protein now differs from the original Beta-Amyloid protein, in that it has greater mass and a different formation, due to the addition of the Tau attachment and peptide fragments. It will therefore respond differently in the blood stream (viscous flow) making it easy to identify by reflected velocity and delivery time.

The device emits individual PEMF low-energy, time-accurate magnetic pulse frequencies which are used to identify the extended protein by its structural surface modification, density and displacement within the viscous flow.

Once the extended protein has been identified it is subjected to a modulation which mimics the mathematical signature of an antibody when marking a pathogen for destruction by neutrophils (White Blood Cells/leucocytes). Using the natural process of the immune system, Neutrophils now destroy the extended protein disguised as a pathogen using a process called Phagocytosis.

So, simply put, our invention is able to identify the extended protein then agitate it such that the body’s own immune system identifies it as an alien form in the blood stream and deals with it as it would any other foreign or invading body.

The housing and/or strap may comprise a shell and/or may be contoured. The housing and/or strap may be semi-rigid; that is, the housing and/or strap may mould to the contour of the patient’s forearm. The housing and/or strap may comprise a cold-moulded polyurethane. The housing and/or strap may be configured such that body temperature (for example a temperature of the forearm of the patient) may be sufficient to mould the strap exactly to a contour of the patient’s forearm. The housing may be sealed, for example to prevent ingress of moisture and/or dirt.

The transducer may be coupled to a patient’s skin via electrodes. The electrodes may comprise pads, and may be locatable on the surface of the skin of the patient (i.e. not to penetrate and/or pierce the skin).

Alternatively or additionally, the device may further comprise a Nano-patch. The Nano-patch may comprise a plurality of Nano-wires. The Nano-wires may be bonded together to form an array of parallel wires. Bonding may be via adhesive. The Nano-patch may be flexible. The Nano-patch may have a thickness of between 2 and 20 microns, in particular between 4 and 10 microns, more particularly approximately 6 microns. Each Nano-wire may have a length approximately equal to a thickness of the Nano-patch. Each Nano-wire may be orientated across the thickness of the Nano-patch. The Nano-wires may comprise magnetic Nano-wires. The Nano-wires may be grown. The Nano-patch may be placed in a cold moulded configuration in the housing.

The device may be configured to transmit an electromagnetic pulse into the forearm of the patient.

The at least one transducer may comprise only one transducer or two, three, four or more transducers. The or each transducer may comprise a magnetic flux transducer. The or each transducer may be driven by a respective chipset comprising multiple layers (e.g. two or three layers).

The control unit may comprise a magnetic flux control unit. The control unit may comprise one or more chip sets, e.g. off-the shelf and/or programmable chipset(s).

The power supply may comprise a battery and/or kinetic energy recovery unit, for generating electrical power from kinetic movement of the patient, and in particular the forearm. The kinetic energy recovery unit may comprise a Nano-frequency kinetic generator.

One or more of the at least one transducer, control unit, and power supply may also be arranged within the housing. However, other arrangements are also possible.

The electromagnetic pulse may comprise at least one electromagnetic pulse, for example only one electromagnetic pulse, or two electromagnetic pulses or more.

The device may be configured to continually transmit an electromagnetic pulse, or a sequence of electromagnetic pulses, at predefined intervals. The intervals may be fixed, variable, or vary in length based on sense signals (e.g. from sensors).

For example, sense signals may be derived from Impedance Spectroscopy, which measures electrical properties of materials, e.g. the conductance (or resistance) and the reactance as a function of applied alternative current frequency, therefore providing a quantitative analysis of the effect of the device on the patient. Alternatively or additionally, four rogue cells that have been extended by a Tau attachment and a peptide inducement which alters the density making them easy to identify by reflected velocity and delivery time.

The electromagnetic modulation may comprise a broad-spectrum frequency set, in particular between 4 and 15 MHz, more particularly between 5 and 12 MHz, more particularly between 6 and 10 MHz. For example, the electromagnetic modulation may span an entire frequency range between 6 and 10 MHz, may include sub frequency ranges spaced between 6 and 10 MHz, and/or may span a frequency range of between 6 and 10 MHz in width.

The electromagnetic modulation (for instance of a single pulse, or within a sequence of pulses) may be emitted over a period of up to 100 microseconds.

In the case of more than one electromagnetic pulse within a sequence of pulses, each electromagnetic pulse may be spaced from another by approximately 100 nanoseconds. This may comprise a spacing of respective peaks of each burst.

The or each electromagnetic pulse may be directed into the patient’s viscous/blood flow, for instance within the radial artery.

Components within the housing may be coated with hard dielectric coatings that may have extremely high damage thresholds.

The device may further comprise diffuse cavity reflectors, which may be arranged to give a high degree of modulations and uniformly, and therefore an optimum burst quality.

In some arrangements, there may be a single Nano-patch for all transducers and/or sensors. In alternative arrangements, there may be separate Nano-patches and/or Nano-wires for some or each of the transducers, transducer layers and/or sensors.

Net vertical electron may be generated in the charged deposition and/or surrounding atoms. The charged particles may result in the creation of electromagnetic modulations. A negative pulse current to the electromagnetic pulse charged electrons may move outward faster in the Nano scale and, the electromagnetic pulse being much heavier, may provide charged ions which may automatically separate the charged bursts. The region closest to the burst point may have a positive charge and, as the burst diminishes, net negative charges may occur, which may cause a swirl in the viscous material (e.g. blood). Separation may occur in the combined charges within the target environment. At one tenth of a microsecond a second burst may attain its maximum strength, which then may fall off and may create movement in the blood flow. Repeated controlled disturbances may result in a net micro electron current.

The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawing(s), which illustrate, by way of example, the principles of the invention. This description is given for the sake of example only, without limiting the scope of the invention. The reference figure(s) quoted below refer to the attached drawing(s).

Figure 1 shows a circuit diagram of a device for destroying extended Beta-Amyloid.

The present invention will be described with respect to certain drawings but the invention is not limited thereto but only by the claims. The drawings described are only schematic and are non-limiting. Each drawing may not include all of the features of the invention and therefore should not necessarily be considered to be an embodiment of the invention. In the drawings, the size of some of the elements may be exaggerated and not drawn to scale for illustrative purposes. The dimensions and the relative dimensions do not correspond to actual reductions to practice of the invention.

Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequence, either temporally, spatially, in ranking or in any other manner. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that operation is capable in other sequences than described or illustrated herein. Likewise, method steps described or claimed in a particular sequence may be understood to operate in a different sequence.

Moreover, the terms top, bottom, over, under and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that operation is capable in other orientations than described or illustrated herein.

It is to be noticed that the term “comprising”, used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. It is thus to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. Thus, the scope of the expression “a device comprising means A and B” should not be limited to devices consisting only of components A and B. It means that with respect to the present invention, the only relevant components of the device are A and B.

Similarly, it is to be noticed that the term “connected”, used in the description, should not be interpreted as being restricted to direct connections only. Thus, the scope of the expression “a device A connected to a device B” should not be limited to devices or systems wherein an output of device A is directly connected to an input of device B. It means that there exists a path between an output of A and an input of B which may be a path including other devices or means. “Connected” may mean that two or more elements are either in direct physical or electrical contact, or that two or more elements are not in direct contact with each other but yet still co-operate or interact with each other. For instance, wireless connectivity is contemplated.

Reference throughout this specification to “an embodiment” or “an aspect” means that a particular feature, structure or characteristic described in connection with the embodiment or aspect is included in at least one embodiment or aspect of the present invention. Thus, appearances of the phrases “in one embodiment”, “in an embodiment”, or “in an aspect” in various places throughout this specification are not necessarily all referring to the same embodiment or aspect, but may refer to different embodiments or aspects. Furthermore, the particular features, structures or characteristics of any one embodiment or aspect of the invention may be combined in any suitable manner with any other particular feature, structure or characteristic of another embodiment or aspect of the invention, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments or aspects.

Similarly, it should be appreciated that in the description various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Moreover, the description of any individual drawing or aspect should not necessarily be considered to be an embodiment of the invention. Rather, as the following claims reflect, inventive aspects lie in fewer than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention.

Furthermore, while some embodiments described herein include some features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form yet further embodiments, as will be understood by those skilled in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the invention may be practised without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.

In the discussion of the invention, unless stated to the contrary, the disclosure of alternative values for the upper or lower limit of the permitted range of a parameter, coupled with an indication that one of said values is more highly preferred than the other, is to be construed as an implied statement that each intermediate value of said parameter, lying between the more preferred and the less preferred of said alternatives, is itself preferred to said less preferred value and also to each value lying between said less preferred value and said intermediate value.

The use of the term “at least one” may mean only one in certain circumstances. The use of the term “any” may mean “all” and/or “each” in certain circumstances.

The principles of the invention will now be described by a detailed description of at least one drawing relating to exemplary features. It is clear that other arrangements can be configured according to the knowledge of persons skilled in the art without departing from the underlying concept or technical teaching, the invention being limited only by the terms of the appended claims.

Figure 1 shows a circuit diagram of a device for targeting and destroying the extended Beta-Amyloid protein, comprising two chipsets DGLP1 and DGLP2, each with eight respective pins (indicated as 1 to 8 on each chipset), of which only seven are used (pin 5 is not used in each case). DGLP1 and DGLP2 may comprise respective 555 timer ICs. The circuit is powered by a 3V DC power source B1, the power being controlled by Switch 2. Resistors R1 to R11, variable resistors P1 to P3, capacitors C1 to C5, diodes D1 to D3, transistors TR1 to TR3 and Switch 1 mediate control signals from the two chipsets DGLP1 and DGLP2 to the electrodes (e.g. conducting pads) E1 and E2 via a transformer T1.

Under typical operation, R1 is 201 kΩ, R3 is 5.01 MΩ, R9 is 167 kΩ, R10 is 6.8 kΩ and C2 is 47 nF. However, in order to tailor the device to a particular user, various different values may be chosen, for instance to suit the user’s blood viscosity. For example, to shift the device to a higher frequency, the following alternative values may be chosen: R1 is 6.8 kΩ, R3 is 167 kΩ, R9 is 236 kΩ, R10 is 9.6 kΩ and C2 is 100 pF. In alternative arrangements, autocalibration may be achieved by the device detecting a patient’s blood viscosity and effectively setting the above-mentioned components to suitable values.

DGLP1 controls emission of electromagnetic impulses (trans-cutaneous pulses) to be delivered to the viscous flow at a pulse rate of between 2-5 Hz.

Reflections of the impulses are interpreted by DGLP2 to determine the relative density of content within the viscous flow and specifically the presence of extended Beta-Amyloid protein in the patient’s viscous flow.

DGLP2 mimics the electrical signals of a pathogen within the immune system, triggering white blood cells to attack and destroy the extended Beta-Amyloid protein.

Switch 1 and Switch 2 are controlled by the algorithms embedded in the device. Switch 1 delivers power from the battery to the circuitry and Switch 2 (when Switch 1 is closed) controls the delivery of pulses into the viscous flow.

Switch 1 and Switch 2 may comprise respective 555 timer ICs, each of which include respective built-in electromagnetic reed switches. It is made from two ferrous reeds encased within a small glass tube-like envelope, which becomes magnetised and moves together when a magnetic field is moved towards the switch. The switch effectively works like a gate, or a bridge, in an electric circuit so when the two reeds are in contact, electricity can flow around the circuit operating the device. Unlike mechanical switches they do not require something or someone to physically flick them on or off, they are controlled completely by being in the close proximity to an invisible magnetic field. Rhodium is used as the contact material in the reed switches due to its low contact resistance and resistance to corrosion.

As the current accesses the reed switch, it becomes a part of an electro ‘magnetic circuit’ that includes the magnetic pulse. The two contacts become ‘opposite magnetic poles’, being attracted and snapping together. It doesn't matter which end of the electromagnetic pulse arrives first as the process is completely controlled by embedded code within DGLP1 and DGLP2: the contacts always polarize in opposite directions to attract and close. As in the drawing the switch is normally open or off, unless the switch is influenced by an electromagnetic pulse, which then switches it on and allows the pulse to flow through it.

In an alternative arrangement not shown in the figures, one or both chipset(s) may comprise a Linux digital embedded Integrated Circuit (IC). One of the ICs is re-triggerable and a monostable multi-vibrator or gated latch; the other is a D flip-flop. The difference between a flip-flop and a gated latch is that in a flip-flop, the inputs are not enabled merely by the presence of a HIGH signal on the CLOCK input.

The re-triggerable monostable multi-vibrator produces pulses depending upon the value of an external capacitor and resistor.

Since the multi-vibrator is a dual IC, it is possible to generate two pulses with ease and exact calibration. These pulses are then separated from each other by increasing the external resistance of one multi-vibrator.

A potentiometer is added in series with the external resistor allowing for the calibration and finite adjustment of the pulse duration times.

These pulses are then used to clock and deliver the D flip-flop sequence, by setting the pulses apart by 20 nanoseconds, which allows the D flip-flop to be clocked high then re-calibrated much lower to around 20 nanoseconds later than the original burst.

The re-triggerable monostable multi-vibrator needs a clock signal to repeat the pulses. A simple embedded timer is used to create a Linux clock tick of 1.3 kHz. The timer is also built with micro potentiometers to allow adjustment of the frequency and duty cycle. All three ICs are powered using a simple kinetic regulator.

Fast rising signals may arrive at the specific components, for instance delivered in nanoseconds.

The PCB layout contains the majority of the components and trace routes required in the invention. Most of the nanosecond switching and pulse generation blocks are laid in further layers.

The first important trace is the clock signal coming from the embedded timer. This trace is routed as directly as possible to allow a good signal path to the re-triggerable monostable multi-vibrator embedded micro-chip.

The remaining traces that require calibration are the pulses from the re-triggerable monostable multi-vibrator which clock and pre-set the D flip-flop in sequence. The length and width of these traces are closely monitored to prevent signal loss or degradation. The external resistor and capacitor are positioned close to the re-triggerable monostable multi-vibrator to create accurate calculated pulses.

These traces were designed to be wide to accelerate the signal quality. Around 100 mils of clearance are needed to prevent arcing between the traces and ground signals. Ground signals are also designed wider than usual to help reduce ground paths interference.

The 20 nanosecond pulse from the pulse generation block is routed directly to the Linux embedded driver with short wide traces, and the input power from the kinetic burst. One switch is used for on/off power and the other turns the pulse generation block on/off. The board is also cut out near the jacks to allow them to sit level with the embedded chip.

Several components are added to the ground traces of the circuit. These allow free paths to the ground plane on the bottom layer.

Signals are generated through two 30 Ω matched transmission lines connected with a switch.

At t<0, a transmission line is kinetically powered to a pre-defined voltage V0.

At t=0, the switch is put to closed state, which results in the propagation of and (reflection) in opposite directions at the switch.

Eventually, both the waves superimpose to give a rectangular pulse, where the amplitude and pulse width can be calculated in a conventional manner.

There may be 4 Nano-wire tubes in an array. The Nano-tubes are also more powerful at the output port running at 15pF average power and peaking at 30pF.

The operation of a further transducer may bring the blood flow back to the optimum temperature, the flow of which may then pass through the brain and stimulate the synapses to dry the previously formed tangles and clumps.

Claims

1. A device for destroying extended Beta-Amyloid protein within the blood of a patient, the device comprising:
a strap for attachment to a forearm of the patient;
a housing attached to the strap;
at least one transducer configured to transmit a pulse into the forearm of the patient;
a control unit configured to:
operate the at least one transducer to emit a pulse;
receive a signal from the at least one transducer indicative of a reflection of the pulse from extended Beta-Amyloid protein within the blood of the patient; and
in response to receiving the signal, operate the at least one transducer to emit electromagnetic modulation that triggers white blood cells to destroy the extended Beta-Amyloid protein within the blood of the patient; and
a power supply for supplying electrical energy to the control unit.

The device of claim 1, wherein the housing is configured such that body temperature is sufficient to mould the strap exactly to a contour of the patient’s forearm.

The device of claim 1 or claim 2, wherein the device further comprises a Nano-patch comprising a plurality of Nano-wires bonded together to form an array of parallel wires.

The device of any preceding claim, wherein the at least one transducer comprises four transducers.

The device of any preceding claim, wherein the power supply comprises a kinetic energy recovery unit, for generating electrical power from kinetic movement of the patient.

The device of any preceding claim, wherein the electromagnetic pulse comprises a sequence of electromagnetic pulses, and the device is configured to continually transmit multiple sequences of electromagnetic pulses.

The device of any preceding claim, wherein the electromagnetic modulation may comprise a broad-spectrum frequency set.

The device of claim 6, wherein the sequence of electromagnetic pulses is emitted over a period of up to 100 microseconds.