US-12623090-B2 - Systems, devices and methods for the treatment of oral and pharyngeal disorders

US12623090B2US 12623090 B2US12623090 B2US 12623090B2US-12623090-B2

Abstract

Herein are provided systems, devices, and methods for the treatment of oral and pharyngeal disorders via the stimulation of pharyngeal muscles. Contraction of the pharyngeal muscle cells ( 9 ) is induced by activation of at least one ion channel ( 1 ) formed in at least one of a muscle cell and a neural cell. The ion channel opens ( 4 ) when it is activated by a stimulus ( 3 ). This allows ions to flow into ( 5 ) and out of ( 6 ) the cell, causing muscle contraction. This muscle contraction can be targeted towards specific muscles depending upon the condition to be treated.

Inventors

Lynne BILSTON
Peter Burke

Assignees

Lynne BILSTON
Peter Burke

Dates

Publication Date: 20260512
Application Date: 20190529
Priority Date: 20180531

Claims (20)

1 . A system comprising: a mechanism configured to form at least one ion channel in at least one of a pharyngeal muscle cell and a neural cell associated with a pharyngeal muscle cell, such that the at least one channel opens and closes in response to a stimulus source; an oral appliance; and a controller operably coupled to the oral appliance and programmed to operate the stimulus source; wherein the oral appliance comprises the stimulus source configured for direct in vivo activation of the at least one ion channel formed in the at least one pharyngeal muscle cell or at least one motor neural cell associated with a pharyngeal muscle cell, thereby causing the at least one ion channel to open and induce contraction of at least one muscle cell; and wherein the oral appliance comprises a channel configured to engage over a user's teeth.
2 . The system according to claim 1 , wherein the at least one channel is photosensitive or magnetically sensitive such that the at least one ion channel opens and closes in response to light or a magnetic field, and the stimulus source provides a stimulus selected from one or more of: light that acts on a cognate optogenetic target; and a magnetic field that acts on a cognate magnetogenetic target.
3 . The system according to claim 2 , wherein the stimulus is light that acts on the cognate optogenetic target; wherein the light is any one of red, amber, blue, or green light; and wherein the ion channel is able to be activated or deactivated by any one or more of red, amber, blue, or green light.
4 . The system according to claim 1 , wherein the system is configured to selectively deliver a control stimulus to the at least one ion channel for selective in vivo activation or deactivation of the at least one ion channel.
5 . The system according to claim 4 , wherein the control stimulus is optical, chemical, genetic, or physical.
6 . The system according to claim 1 , wherein the at least one ion channel is only formed in at least one location selected for muscle cell stimulation.
7 . The system according to claim 1 , wherein the stimulus is delivered only to ion channels formed in at least one location selected for muscle cell stimulation and not to an ion channel formed in any other location.
8 . The system according to claim 1 , including at least one sensor for monitoring at least one predetermined treatment situation of a user, wherein the at least one predetermined treatment situation is selected from: the respiratory cycle of the user, breathing, cessation of breathing, apnea, hypopnea, diaphragm movement, muscle cell activity, neural cell activity, impedance across chest, chest movement, abdominal movement, airway pressure, temperature, pharyngeal narrowing, or pharyngeal collapse.
9 . The system of claim 8 , wherein the at least one sensor is an accelerometer for detecting vibrations of the airway.
10 . The system according to claim 1 , wherein at least part of the oral appliance is implantable.
11 . The system of claim 1 , wherein the oral appliance is an orthodontic retainer or orthodontic plate.
12 . The system of claim 1 , wherein the oral appliance further comprises a releasable fastening mechanism to hold the oral appliance in an oral cavity of the user.
13 . The system of claim 1 further comprising a plurality of intraoral delivery sites positioned proximate to a pharyngeal muscle cell or a neuron associated with a pharyngeal muscle cell and configured to deliver the direct, in vivo stimulus to at least one ion channel; wherein the stimulus source is operably connected to the delivery sites to provide the stimulus directly at or through the delivery sites.
14 . The system of claim 1 , wherein the stimulus source is configured for direct, in vivo activation of at least one ion channel formed in at least one human pharyngeal muscle cell or at least one human motor neural cell associated with a human, pharyngeal muscle cell.
15 . The system of claim 1 , wherein the mechanism is configured to deliver genetic material to the at least one pharyngeal muscle cell or at least one motor neural cell associated with a pharyngeal muscle cell, thereby forming the at least one ion channel.
16 . The system of claim 15 , wherein the mechanism is configured to inject a viral vector into the at least one pharyngeal muscle cell or at least one motor neural cell associated with a pharyngeal muscle cell or electroporate the at least one pharyngeal muscle cell or at least one motor neural cell associated with a pharyngeal muscle cell.
17 . The system of claim 1 , wherein the mechanism is configured to deliver nanoparticles to the at least one pharyngeal muscle cell or at least one motor neural cell associated with a pharyngeal muscle cell, thereby forming the at least one ion channel.
18 . A system for inducing contraction of at least one pharyngeal muscle cell, the system including: a mechanism configured to form at least one ion channel that is photosensitive or magnetically sensitive in at least one of a pharyngeal muscle cell and a neural cell associated with a pharyngeal muscle cell; an oral appliance configured to deliver an in vivo stimulus to the at least one ion channel formed in the at least one of a pharyngeal muscle cell and a neural cell associated with a pharyngeal muscle cell, thereby to induce contraction of at least one muscle cell; a stimulus source, configured to provide the stimulus through the oral appliance; and a controller operatively coupled to the stimulus source and programmed to operate the stimulus source; wherein the stimulus is selected from one light that acts on a cognate optogenetic target comprising the at least one ion channel and a magnetic field that acts on a cognate magnetogenetic target comprising the at least one ion channel.
19 . A method for inducing contraction of at least one pharyngeal muscle cell in a human subject, the method including the steps of: forming at least one ion channel that is photosensitive or magnetically sensitive in at least one of a pharyngeal muscle cell and a motor neural cell associated with a pharyngeal muscle cell in the human subject; and delivering an in vivo stimulus directly to the at least one ion channel thereby causing the at least one ion channel to open and induce contraction of at least one muscle cell; wherein the stimulus is selected from one or more of: light that acts on a cognate optogenetic target comprising the at least one ion channel; and a magnetic field that acts on a cognate magnetogenetic target comprising the at least one ion channel; and detecting at least one predetermined treatment situation of the human subject, and thereafter performing the step of delivering the stimulus, wherein the at least one predetermined treatment situation is selected from: the respiratory cycle of the user, breathing, cessation of breathing, apnea, hypopnea, diaphragm movement, muscle cell activity, neural cell activity, impedance across chest, chest movement, abdominal movement, airway pressure, temperature, pharyngeal narrowing, or pharyngeal collapse.
20 . The method according to claim 19 , wherein the stimulus is light that acts on a cognate optogenetic target; wherein the light is any one of red, amber, blue, or green light; and wherein the ion channel is able to be activated or deactivated by any one or more of red, amber, blue, or green light.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS The present application is a U.S. national stage application under 35 U.S.C. § 371 of PCT Application No. PCT/AU2019/050532, filed May 29, 2019, which claims priority to Australian Patent Application No. 2018901953, filed May 31, 2018. The disclosures of the aforementioned priority applications are incorporated herein by reference in their entireties. FIELD OF THE INVENTION The present invention relates to systems, devices and processes for intervention in oral and pharyngeal disorders. However, it will be appreciated that the invention is not limited to this particular field of use. BACKGROUND OF THE INVENTION Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field. Activation of excitable cells, such as neurons and muscle cells, can be achieved via the introduction of receptors or ion channels in these cells that respond to stimuli that are not usually present in the normal animal (including humans). These receptors and ion channels can be designed or selected to respond to non-physiological stimuli, such as light (optogenetics), chemical substances (chemogenetics), or a magnetic field (magnetogenetics), for example. Optogenetics is the use of light to stimulate excitable cells, by genetically modifying these cells to express light-sensitive ion channels, or opsins, in their membranes. Chemogenetics is the use of artificially engineered receptors that respond to non-physiological chemical stimuli to activate the excitable cells. Magnetogenetics is the use of magnetic stimuli to stimulate the excitable cells, by genetically modifying these cells to express magnetically sensitive ion channels in their membranes. The pharyngeal muscles surround the upper airway and are responsible to a range of critical functions including speech, swallowing, and maintaining patency of the upper airway, enabling respiration. Obstructive sleep apnoea is a common sleep disorder in which muscle activity of the pharyngeal muscles is insufficient to maintain patency of the upper airway during sleep. The upper airway collapses repeatedly during sleep resulting in oxygen desaturation, that requires arousal to normalize. The results in sleep fragmentation, daytime sleepiness, increased risk of accidents and cardiovascular disease. Stimulation of the pharyngeal dilator muscles can widen the airway and maintain patency, including during sleep. There are current treatments that rely on electrical stimulation of the dilator muscles in the tongue, whereby electrical stimulation activates the hypoglossal nerve, thereby causing the dilator muscles to contract and widen the upper airway. These systems are fully implanted and cannot provide non-invasive or minimally invasive muscle stimulation. Additionally, they are not effective for all people. Other treatment methods, such as the delivery of continuous positive airway pressure or mandibular advancement splints, have reports of sub-optimal patient tolerance and adherence, or non-universal effectiveness. Dysphagia is difficulty in swallowing. It may occur with or without pain. It can occur for many reasons but is commonly associated with neurological dysfunction of the pharyngeal or oesophageal muscles. This can occur in a range of neurological disorders, including multiple sclerosis, muscular dystrophy, Parkinson's disease, stroke, and spinal cord or brain injury. It can also occur after trauma or surgery, or in cancer, or as a result of cancer treatments. Current treatments involve physical therapy exercises, or surgical or pharmaceutical treatments that relax the oesophageal muscles to reduce distal blockage of the oesophagus. Speech disorders involve difficulties in speaking or producing sounds fluently. A subset of patients with speech disorders acquire these as a result of dysfunction of the pharyngeal muscles, associated with neurological disorders such as stroke, or neuromuscular degenerative disorders. It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative. SUMMARY OF THE INVENTION Herein are provided systems, devices, and methods for the treatment of oral and pharyngeal disorders. In some preferred embodiments, light-responsive opsin proteins able to activate either motor neurons innervating the pharyngeal muscle(s) or the muscle cells themselves are used, thereby inducing contraction of the pharyngeal muscles in response to a light stimulus. In other preferred embodiments, magnetic or chemical stimulus are used to induce contraction of the pharyngeal muscles. According to a first aspect, the present invention provides a system for stimulating pharyngeal muscles, the system including means for activation of at least one ion channel formed in at least one of a muscle cell and a neural cell. Accordi