HK40000749A - Collecting physical therapy information to enhance treatment efficacy of botulinum toxin - Google Patents

Description

Collecting information on physical therapy to enhance the therapeutic effect of botulinum toxin

Technical Field

The present invention relates generally to improving active motor capacity in a subject, and more particularly to using prescribed physical therapy regimens in conjunction with a Clostridial neurotoxin, such as a botulinum toxin, to reduce symptoms associated with impaired or abnormal active motor capacity.

Background

Abnormal motor abilities include muscle rigidity or stiffness, tightness, contracture, spasm (i.e., an involuntary movement with an unsmooth sensation), dystonia, hypertonia, and clonus (i.e., repeated involuntary movements or reflexes). Abnormal motor capacity is often associated with neurological disorders including stroke, cerebral palsy, muscular dystrophy, spinal cord injury, brain injury, spastic disorders such as blepharospasm, spastic torticollis (cervical dystonia), oromandibular dystonia, and spastic dysphonia (laryngeal dystonia), as well as neurodegenerative diseases such as multiple sclerosis and parkinson's disease. It may also be associated with various other metabolic disorders, muscle diseases, upper or lower motor neuron disorders, and Guillain-Barre syndrome.

In addition to possibly causing pain, symptoms associated with abnormal muscle tone may interfere with a person's ability to voluntarily move and perform daily activities. Physical therapy of stretching and active exercise is a recognized treatment for abnormal muscle tone. Additional information on how Physical Therapy can be used to treat motor ability caused by neuromotor disorders Is in Veerbeek, JanneMarieke et al, "What Is the epidemic for Physical Therapy Poststroke @, Vol.9: 2, PLOS One, 2014 @? A Systematic Review and Meta-Analysis, "the disclosure of which is incorporated herein by reference.

In addition to physical therapy, it may be helpful to administer a toxin (such as botulinum toxin) to the affected muscle. For example, when injected into muscle, botulinum toxin binds rapidly and strongly to presynaptic cholinergic nerve terminals and inhibits exocytosis of acetylcholine from the nerve terminals to muscle fibers. This results in partial paralysis of the muscle afflicted by the spasm, which in turn results in relaxation.

Botulinum toxin is useful for treating various types of neurological disorders, including movement disorders associated with central nervous system injury or disease (such as trauma, stroke, multiple sclerosis, parkinson's disease and cerebral palsy), cervical dystonia (spasmodic torticollis), blepharospasm, hyperhidrosis, chronic daily headache, strabismus, esophageal achalasia and focal dystonia. For additional information on how botulinum toxin can be used for spasticity treatment, please refer to Simpson d.m. et al, Neurology 6; 70(19), 1691, 1698 page (2008), "Association: Botulinum neuron for the transmission of therapeutics (an evaluation-based review)" Report of therapeutics and Technology Association of the American academy of therapeutics ", the disclosure of which is incorporated herein by reference.

Disclosure of Invention

A method for improving active locomotor capacity of a subject is provided. The method comprises the following steps: administering to a subject in need thereof a first botulinum toxin treatment to a muscle affected by an impaired voluntary motor ability. In some embodiments, the method further comprises instructing the subject to undergo physical therapy comprising physical activity involving the affected muscle. In embodiments, the method further comprises instructing the subject to record information associated with the physical therapy. In some embodiments, the physical therapy information is recorded by the subject, for example in a log or diary. In other embodiments, the physical therapy information is entered into a software program operating on a computer device, and the physical therapy information is stored in a database. In some aspects, the subject enters the physical therapy information into a log or diary, or into a software program. Botulinum toxin therapy can be administered or received into the affected muscle, for example, by injection. The treatment may also be administered or received into the neuromuscular junction of the affected muscle, for example by injection.

The method may further comprise: accessing physical therapy information of a subject; designing a treatment regimen based at least in part on the physical therapy information of the subject; and administering a second botulinum toxin therapy to the subject according to the treatment regimen, wherein the botulinum toxin therapy is sufficient to treat the impaired voluntary locomotor ability of the subject.

In some embodiments, the physical therapy information is received by a software program operating on a first computer device, and the physical therapy information is stored in a database on the first computer device or a second computer device in communication with the first computer device. In some embodiments, the subject enters the physical therapy information into a software program.

In some embodiments, the method may further comprise: reviewing physical therapy information of the subject (e.g., by accessing physical therapy information stored in a database); designing a treatment regimen based at least in part on the physical therapy information of the subject; and administering a second botulinum toxin treatment to the subject according to the treatment regimen, wherein the botulinum toxin treatment is sufficient to treat impaired voluntary locomotion.

In another embodiment, in a method for improving voluntary locomotor ability in a subject using a botulinum toxin, the improvement comprises: determining an appropriate botulinum toxin treatment based on a physician's assessment of how a subject responds to a prescribed physical therapy regimen comprising: (i) administering or receiving botulinum toxin to improve voluntary locomotion; (ii) instructing the subject to participate in a physical activity involving a muscle affected by the impaired voluntary motor ability, or to participate in a physical activity involving a muscle affected by the impaired voluntary motor ability; and (iii) instructing the subject to record information associated with the physical therapy, or to record information associated with the physical therapy. In some embodiments, the physical therapy information is received by a software program operating on a computer device and the physical therapy information is stored in a database associated with the computer device. In some embodiments, the subject enters the physical therapy information into a software program.

In another embodiment, the method includes receiving a first botulinum toxin treatment to improve voluntary motor capacity of a muscle affected by an impaired voluntary motor capacity; performing a physical therapy comprising a physical activity involving the affected muscle; and recording information associated with the physical therapy. In some embodiments, the physical therapy information is received by a software program operating on a first computer device and the information is stored in a database on the first computer device or a second computer device in communication with the first computer device. In some embodiments, the subject enters the physical therapy information into a software program. The method can further include receiving a second botulinum toxin treatment, wherein the second treatment is determined based at least in part on the physical therapy information.

In another embodiment of the present invention, a computer system is provided. The computer system is programmed to perform the steps of a computer-implemented method comprising: receiving information associated with physical therapy from a subject undergoing physical therapy and botulinum toxin treatment for impaired voluntary motor ability; storing the physical therapy information in a database; and transmitting the physical therapy information to the physician. In one embodiment, the physician has previously administered a botulinum toxin treatment to the subject.

In another embodiment, a non-transitory computer-readable storage medium storing instructions is provided. The non-transitory computer readable medium, when executed by a computer system, causes the computer system to perform the steps of a computer-implemented method, the method comprising: receiving information associated with physical therapy from a subject undergoing physical therapy and botulinum toxin treatment for impaired voluntary motor ability; storing the physical therapy information in a database; and transmitting the physical therapy information to the physician. In one embodiment, the physician has previously administered a botulinum toxin treatment to the subject.

Drawings

FIG. 1 shows a subject 10 being administered a dose of botulinum toxin by injection 12.

Fig. 2 shows subject 10 inputting physical therapy information into tablet computer 14, tablet computer 14 communicating with host server computer 22 via network link 20.

Fig. 3 shows a physician 30 operating a computer 32, the computer 32 communicating via a communication link 24, the communication link 24 communicating with a host computer system 22 that stores information input by the subject.

Detailed Description

The present invention is useful for clinical management of subjects with impaired voluntary motor abilities. Impairment of active motor capacity may be the result of, for example, abnormal muscle hyperactivity in the subject. The subject may have any of various types of medical conditions associated with impaired voluntary motor abilities, including stroke, cerebral palsy, muscular dystrophy, spinal cord injury, brain injury, spastic disorders such as blepharospasm, spastic torticollis (cervical dystonia), oromandibular dystonia, and spastic dysphonia (laryngeal dystonia), as well as neurodegenerative diseases such as multiple sclerosis and parkinson's disease.

The affected muscles may be anywhere within the subject's body, including in the upper limbs (adult or pediatric), such as the shoulders, arms, or hands; in the lower extremities (adults or children), such as in the legs or feet; or in the bladder (e.g., as affected in neurogenic detrusor over activity (NDO)). The term "affected muscle" as used herein refers to any muscle affected by impaired voluntary motor abilities. With appropriate treatment, the subject may experience various improvements in active motor abilities, such as increased mobility, increased flexibility, increased strength, increased passive or active range of motion of the affected limb, reduced pain, and the ability to independently perform activities of daily living.

In the present invention, botulinum toxin is administered to a subject in conjunction with specifically defined physical therapy techniques. Administration of botulinum toxin is typically performed by a medical professional. As used herein, the term "medical professional" includes a clinician, physician, nurse, medical technician, or the like. In some embodiments, the subject may self-administer a botulinum toxin. The botulinum toxin can be administered in any suitable manner, such as by transdermal administration or injection into the affected muscle or the neuromuscular junction of the affected muscle.

In the present invention, the botulinum toxin producing strain is preferably Clostridium botulinum (Clostridium), but is not limited thereto, and it is apparent to those skilled in the art that any strain capable of producing botulinum toxin can be used in the present invention. As used herein, the term "botulinum toxin" is meant to include not only neurotoxins produced by strains of clostridium botulinum, but also any modified, recombinant, hybrid, fused and chimeric botulinum toxins. The modified or recombinant botulinum toxin can have light and/or heavy chains produced recombinantly by a non-clostridial species. Furthermore, the term "botulinum toxin" as used herein is meant to include any and all known botulinum toxin serotypes, including serotypes A, A1, A2, A3, A4, B, C, C1, D, E, F, and G, as well as botulinum toxin complexes (e.g., 300, 600, and 900kDa complexes) and pure botulinum toxins (e.g., 150kDa neurotoxic molecules), all of which can be used in the practice of the present invention. For additional information on the properties of various botulinum toxins, see Simpson d.m. et al Neurology 6; 70(19), 1691, 1698 page (2008), "Association: Botulinum neuron for the transmission of therapeutics (an evaluation-based review)" Report of therapeutics and Technology Association of the American academy of therapeutics ", the disclosure of which is incorporated herein by reference.

In one embodiment of the present invention, the botulinum toxin administered to the subject is a type a toxin. Botulinum toxin type A1 complex, for example, under the trade name botulinum toxinAndand (5) selling. In another embodiment of the invention, the botulinum toxin used is, for example, under the trade name botulinum toxinAndtoxin type B is sold. In other embodiments of the present invention, the botulinum toxin used is any other known toxin type, including A1, A2, A3, A4, C, C1, D, E, F, or G.

Botulinum toxin is obtained commercially by establishing and culturing a c. botulinum culture in a fermentor and harvesting and purifying the fermentation mixture according to known techniques. The botulinum toxin in "A" form is currently commercially available from several sources, for example under the trade name botulinum toxinAvailable from Ipsen biopharmaceutical Co., Ltd under the trade nameObtained from Merz by the tradenameObtained from Medyox Limited and under the trade nameObtained from Allergan ltd.

The biological activity of botulinum toxin is involved, for example, in the inhibition of neurotransmission at synapses at neuromuscular junctions, resulting in muscle paralysis or inhibition of exocytosis, particularly of acetylcholine or another neurotransmitter. The biological activity of botulinum neurotoxin is related to its proteolytic activity. Thus, one method of determining the biological activity of any botulinum toxin is to measure proteolytic activity on the relevant matrix as described above. Assays useful for determining this activity are known in the art; one such assay is described in WO 95/33850, the disclosure of which is incorporated herein by reference.

Botulinum toxin can be administered by any means known in the art, including direct injection into the affected muscle (i.e., intramuscular injection), injection into the neuromuscular junction of the affected muscle, subcutaneous injection, or transdermal administration.

Targeting the neuromuscular junction may increase the effectiveness of botulinum toxin therapy and/or allow for the use of lower concentration doses of botulinum toxin, such as Gracies JM, Lugassy M, Weisz DJ, Vecchio M, Flanagen S, Simpson DM in Arch Phys Med Rehabil 2009, 90: 9-16, "a double-blank controlled stuck," the disclosure of which is incorporated herein by reference. In some embodiments, the botulinum toxin is injected into the neuromuscular junction.

Transdermal administration allows the toxin to be delivered to a target site associated with impaired voluntary motor ability to provide a therapeutic effect, such as a reduction in muscle relaxation or muscle spasm, without the difficulties and discomfort associated with needle injection of botulinum toxin. If desired, an adhesive patch containing an amount of botulinum toxin sufficient to improve voluntary locomotor ability can be self-administered by the subject based on the direction of the physician. The use of adhesive patches for transdermal delivery of therapeutic drugs is described, for example, in New Eng J Medicine, 325(5), Tonnesen, p. et al, 8 months 1991; 311-315, "A double blue tertiary of a 16-hour transmammalian patch in a labeling process," the disclosure of which is incorporated herein by reference.

Botulinum toxin can be present as a sterile pyrogen-free aqueous solution or dispersion, or as a sterile powder for reconstitution into a sterile solution or dispersion. If desired, tonicity adjusting agents such as sodium chloride, glycerin and/or various sugars may be added. Stabilizers may be included if desired. The formulations may be preserved by means of any suitable pharmaceutically acceptable preservative, such as parabens.

In some embodiments, the botulinum toxin is formulated in unit dosage form, for example as a sterile solution in a vial, or as a vial or sachet containing a lyophilized powder, for reconstitution in a suitable carrier (such as saline) for injection. In one aspect, botulinum toxin is formulated in a solution containing saline and pasteurized human serum albumin, which stabilizes the toxin. The solution can be sterile filtered, filled into individual vials, and then vacuum dried to obtain a sterile lyophilized powder. In use, the powder can be reconstituted by addition of sterile, preservative-free physiological saline (0.9% sodium chloride for injection). Alternatively, commercially available sterile botulinum toxin powder can be incorporated into a polymeric matrix of a suitable carrier using known methods and formed into an adhesive patch for use in combination with a skin permeation enhancer such as dimethyl sulfoxide (DMSO) or azone (1-dodecylazacycloheptane-2-one).

Generally, the amount of botulinum toxin administered to the subject is sufficient to ameliorate the impairment of the voluntary motor capacity of the affected muscle or muscles. The amount of botulinum toxin will depend on a number of factors including the severity of the disease, the number of muscle groups in need of treatment, the age, size and/or sex of the subject, and the type and potency of the particular toxin. The potency of toxins may be expressed as LD₅₀Multiples of the value. One LD₅₀The unit is an equivalent amount of toxin that causes 50% (half) of the deaths of a group of test animals, such as laboratory mice. Alternative methods of determining toxin potency may also be utilized, including, for example, European Pharmacopoeia monograph (European Pharmacopoeia monograph) 01/2005: 2113, which is incorporated herein by reference.

The dose administered to the subject is an amount effective to improve voluntary locomotor ability. For example, regardless of the type of botulinum toxin or regardless of its source, the amount can be between 0.01 units and 1000 units of botulinum toxin. Smaller or larger doses may be administered where appropriate. In some embodiments, the dose of botulinum toxin is between about 1 unit and about 500 units per intramuscular injection. For example, the dose can be about 1 unit, 50 units, 100 units, about 150 units, about 200 units, about 250 units, about 300 units, about 350 units, about 400 units, about 450 units, or about 500 units. In one embodiment, up to 1000 units of angiotoxin a are administered to a subject with impaired active motor ability (e.g., a patient with spastic paralysis)Additional information regarding the appropriate dosage of Botulinum Toxin is found in Jaben, Afshan et al, at Vol.2011.7/14 (suppl.1) at pp.31-34 of Jaben Indian Acad neuron, Guidelines for the use of botulin Toxin in kinetic disorders and activity, and in Ozcakir, Suheda et al, at Clin Med.Res.2007, pp.5 (2) at pp.132-138 of botulin Toxin in poststructure activityDescribed in the publications, the disclosure of which is incorporated herein by reference.

Depending on the potency of the botulinum toxin and its duration of action, intermittent dosing may be required. Ultimately, however, the amount of toxin administered and the frequency of its administration will be at the discretion of the physician responsible for the treatment, and will be commensurate with safety concerns and the effects produced by the toxin.

Recent studies have shown that subjects experiencing post-stroke spasticity can benefit by receiving early botulinum toxin treatment. See, for example, Verplancke et al, Clin Rehabil, 2005; 19: 117- "A random mixed controlled three of boron toxin on lower limb vibration property felt reached zero resultant wind broad in Jury"; cousins et al 2010 to Clin Rehabil; 24: 501? A phase II random controlled pilot stuck to estimatateffect size, "Clin Rehabil 2010; 24: 501-513); hesse et al 2012 to Clin Rehabil; 26: 237-; rosales et al 2012 in neuroehabil Neural Repair; 26: 812-; and 2014 to Eur JNeurol, Fietzek et al; 21: 1089-; the disclosures of which are incorporated herein by reference. Thus, in some embodiments of the method, a subject experiencing symptoms of impaired voluntary motor ability (e.g., spasticity) caused by a stroke receives botulinum toxin treatment early, for example, within one year of the stroke. For example, a subject having a stroke may be administered his or her first botulinum toxin treatment within 9 months, 6 months, 3 months, 2 months, 1 month, 3 weeks, 2weeks, 1 week, or even several days after having had the stroke.

Successful treatment of impaired voluntary motor capacity with botulinum toxin can be determined using routine methods known to those of ordinary skill in the art. For example, successful treatment may be associated with improved voluntary motor ability, reduced muscle tone, reduced pain, reduced spasticity, reduced deformity, and the like. The determination may be made by the subject, one or more medical professionals, or a combination of both.

In the present invention, the subject is involved in physical therapy in conjunction with botulinum toxin treatment. The physical therapy includes one or more physical activities or techniques involving the affected muscle, such as exercising, stretching, contracting and relaxing, joint mobilization, myofascial release techniques, heating or cooling the affected muscle, training the affected muscle, performing an alternating motion of the affected muscle, casting/orthotics, and/or positioning the affected muscle (e.g., prone, standing, or sitting). Additional information on the type of Physical Therapy activity that can be used to treat neurological movement disorders Is found in Veerbeek, JanneMarieke et al, PLOS One, at month 2 2014, 9:2, Vol. 87987, "What Is the event for Physical Therapy Poststroke? Described in the scientific Review and Meta-Analysis section, the disclosure of which is incorporated herein by reference.

In some embodiments, a treatment regimen will be determined for the subject. As used herein, the term "treatment regimen" refers to one or more types of treatment that a subject is undergoing to improve voluntary locomotion capacity, including botulinum toxin treatment, physical therapy, or a combination of both.

In one embodiment, a treatment regimen will be determined based at least in part on individual jobs and periodic reports of the subject (e.g., patient). In one aspect, the subject is treated according to a Guided Self-rehabilitative contract (GSC). This strategy aims to create and maintain motivation for the patient to be able to use physical therapy techniques, such as stretching and training, for long periods and in large quantities. This may result in substantial functional improvement in the chronic phase. In such a contract, the therapist acts as a coach, for example: by selecting and teaching the required exercise for the patient for at least one year in infrequent, thorough visits (e.g., each month); and psychological support to encourage patient compliance. In some embodiments, the subject visits the physician at least two or more times over the course of a year; in some cases, three or more times over the course of a year; in some cases, four or more times over the course of a year; in some cases, five or more times over the course of a year; and in some cases six or more times over the course of a year.

The patient, in turn, agreed to perform the prescribed daily stretching postures and maximum amplitude alternating movements over the long term, and recorded the work in a written diary. To facilitate such contracts, manuals and applications for cell phones and tablet computers may be used. Additional information regarding The guided self-healing contract strategy is described in "controlled' Autotoreduce guide data la person space" by Gracies et al in Association neuroco, Paris ISBN 978-2-35327 169-6(2013) and "The Concept of guided seat-renewal controls in The development strategy" by Gracies et al in 25(03) (2015) of Physikalische medicinal development strategy Kurortemez, The disclosures of which are incorporated herein.

In some embodiments, the subject is regularly instructed by a physician and/or therapist. A physician and/or therapist may select and impart physical activity to the subject. The physician and/or therapist may also provide encouragement to the subject, which in turn leads to improved compliance with physical therapy and contributes to the subject's improved voluntary motor abilities.

In some embodiments, the methods of the present invention comprise administering to a subject a first botulinum toxin treatment to a muscle affected by an impaired voluntary motor capacity; and instructing the subject to perform a physical therapy comprising physical activity involving the affected muscle. Another embodiment of the present invention is an improvement on the method, comprising: the subject is instructed to record information associated with the physical therapy. In some embodiments, the physical therapy information is recorded (e.g., by the subject) into a log or diary. In other embodiments, the physical therapy information is recorded (e.g., by the subject) into a software program. The software program may be operable on a first computer device and the physical therapy information is stored in a database on the first computer device or on a second computer device in communication with the first computer device.

In some embodiments, the method further comprises: reviewing physical therapy information of the subject (e.g., by accessing physical therapy information stored in a database); designing a treatment regimen based at least in part on the physical therapy information of the subject; and administering a second botulinum toxin therapy to the subject according to the treatment regimen, wherein the botulinum toxin therapy is sufficient to treat impaired voluntary locomotion.

In another embodiment, in a method for improving voluntary locomotor ability in a subject using a botulinum toxin, the improvement comprises: determining an appropriate botulinum toxin treatment based on an evaluation of how the subject responds to a prescribed physical therapy regimen comprising: (i) administering botulinum toxin to improve voluntary motor capacity of a muscle affected by impaired voluntary motor capacity; (ii) engaging in at least one physical activity involving the affected muscle; and (iii) recording information associated with the physical therapy. In some embodiments, the physical therapy information is recorded into a log or diary. In other embodiments, the physical therapy information is recorded in or by a software program operating on the computer device, and the physical therapy information is stored in a database associated with the computer device. In some embodiments, the subject records physical therapy information.

In another embodiment, the method comprises: receiving a first botulinum toxin treatment to improve voluntary motor capacity of a muscle affected by the impaired voluntary motor capacity; performing a physical therapy comprising at least one physical activity involving the affected muscle; and recording information associated with the physical therapy. In some embodiments, the physical therapy information is recorded by the subject into a log or diary. In other embodiments, the physical therapy information is recorded into or by a software program operating on a first computer device, and the information is stored in a database on the first computer device or a second computer device in communication with the first computer device. The method can additionally include receiving a second botulinum toxin treatment, wherein the second treatment is determined based at least in part on the physical therapy information.

In some embodiments of the invention, clinical management of impaired voluntary motor ability of a subject is enhanced due to the fact that information about physical therapy is recorded into a log or diary or into a software program capable of receiving and transmitting information about physical therapy. In some aspects of the invention, motivation of the subject is improved as a result of recording the physical therapy information. As used herein, the term "motivation" refers to the desire or willingness of a subject to continue participating in physical therapy. The act of recording the physical therapy information may, for example, result in the subject being more likely to continue to participate in physical therapy, or to participate in more physical therapy, or for a longer period of time. In some embodiments, the act of recording physiotherapy information results in the subject actually participating in more physiotherapy than he or she would otherwise be involved in his or her unrecorded physiotherapy information. In some embodiments, the motivation for the improvement of the subject resulting from recording the physical therapy information is at least partially responsible for improving the active motor capacity of the subject.

In some aspects, the improvement in the active motor capacity of the subject is substantial. Improved techniques for measuring voluntary locomotor ability are well known in the art and include, for example, modified Ashworth degrees (MAS), Tardieu degrees (TS), and Triple Spasticity (TSs). Additional information on how to measure active motor capacity is described in "Reliability of a new scale for measurement of kinetic in stroke properties" by Li et al, 46(8), 746-53(2014) to j.

In some embodiments, the physical therapy is appropriate for the particular subject. In some embodiments, the subject is instructed to undergo physical therapy and/or is instructed to record information associated with physical therapy on a regular basis, such as three times a day, twice a day, once a day (daily), twice a week, or weekly. As a result, the subject may participate in physical therapy and/or record information associated with physical therapy on a regular basis, such as three times a day, twice a day, once a day (daily), twice a week, or weekly.

In other embodiments of the invention, the software program is used in conjunction with botulinum toxin treatment and/or physical therapy (such as the GSC strategy). In these embodiments, the physician and/or therapist instructs the subject to use a software program that receives information associated with the physical therapy. The software program is run on any suitable computer device. The software program may receive various information such as the type of physical therapy activity performed, the duration of the physical therapy activity, the frequency of the physical therapy activity, symptoms related to impaired active motor capacity (e.g., degree of pain or stiffness, frequency of muscle spasms, duration of muscle spasms, range of motion, etc.), the effect of the physical therapy activity (if any), and any other comments regarding the physical therapy activity. The software program receives information associated with the physical therapy of the subject and stores the information in a database. The database may reside on the same computer device used by the subject, or on a different computer device capable of communicating with the computer device used by the subject.

In some embodiments, the physician reviews the physical therapy information. Using a computer device capable of communicating with the database, the physician can access the physical therapy information. In one aspect, after reviewing the information, a physician (e.g., clinician) uses the information to determine an appropriate treatment regimen, or to make or suggest adjustments to an existing treatment regimen. In another aspect, the physician uses the physical therapy information to determine or alter a botulinum toxin treatment, i.e., a pattern, amount, or frequency of botulinum toxin administration to the subject. The determination will take into account various factors, including physical therapy information, to arrive at an optimal treatment regimen for the subject.

As used herein, the term "optimal treatment regimen" refers to a treatment regimen determined by a physician to be optimal for a particular subject based on various factors including the age, size and/or sex of the subject, the muscle group in need of treatment, the efficacy of toxins, the physical therapy activities performed by the subject, the duration and frequency of these physical therapy activities, the symptoms of the subject associated with impaired voluntary motor abilities, and information related to physical therapy activities. An optimal treatment regimen may include administration of botulinum toxin to the affected muscle, prescription of physical therapy activity (e.g., within the GSC strategy), or a combination of both. In one aspect, an optimal treatment regimen comprises a prescription for physical therapy followed by administration of an amount of botulinum toxin sufficient to improve voluntary motor capacity of one or more affected muscles.

As used herein, the term "computer device" refers to any electronic device that stores and processes data, typically in binary form, according to instructions given in a software program, and includes, for example, a desktop, laptop, or tablet personal computer; "netbook" for surfing; mobile communication devices, such as smart phones; a personal digital assistant; a portable audio or video file player; a portable game machine; a portable electronic reader or equivalent device. The computer device may communicate with another computer device over any suitable type of network, such as the internet, and may use any suitable protocol, medium (e.g., fiber optic, coaxial, wireless broadband, etc.), network interface, or bandwidth.

The computer device used by the subject may be the same or different from the computer device used by the physician to access the physical therapy information. In some embodiments, the computer device used by the subject is the same computer device that the physician uses to access the physical therapy information. For example, the subject may enter physical therapy information into his/her smartphone and take the smartphone to a clinic for a visit so that the doctor views the information directly from the smartphone. In other embodiments, the computer device used by the physician to access the physical therapy information is different from the computer device used by the subject to input the physical therapy information. For example, the subject may enter physical therapy information into a web portal specifically designed to collect that type of information, and the physician uses his/her own desktop computer to access the web portal and view the information that the subject has entered. In another example, the subject may wear a portable electronic device (e.g., a smart watch or a body-mounted fitness tracker) that records the subject's physical therapy activity and transmits this information to the subject's computer device.

The computer device on which the database resides may be the same or different from the computer device used by the subject to receive the physical therapy information and/or the computer device used by the physician to access the information. In some embodiments, the database is on a computer device different from both the computer device used by the subject to receive the physical therapy information and the computer device used by the physician to access the information. For example, the subject may enter information into a web portal via their laptop computer. This information is stored on a web server computer which is then accessed by the physician on his/her own computer to view the physical therapy information.

In some embodiments, the invention is a software product. As used herein, the term "software product" refers to a non-transitory computer-readable storage medium storing instructions that, when executed by a computer system, cause the computer system to perform the steps. The software product may reside on any suitable computer readable storage medium such as CD-ROM, DVD, memory, hard disk, flash drive, RAM, ROM, cache, etc. The software platform used to implement the present invention may vary depending on design considerations, such as user preferences, cost, implementation, ease of use, machine capabilities, network limitations, and the like.

In some embodiments, a computer system is provided. A computer system programmed to perform the steps of a computer-implemented method, the system comprising: receiving information associated with physical therapy from a subject undergoing physical therapy and botulinum toxin treatment for impaired voluntary motor ability; storing the physical therapy information in a database; and sending physical therapy information to a physician who has administered botulinum toxin treatment to the subject.

In some embodiments, the invention is a computer system comprising one or more computer devices programmed to perform the methods of the invention. The hardware platforms used by the subject, the physician, and/or any other third party may be different, but operate together as a system. For example, the subject being treated may use his/her own computer device to enter physical therapy information, which may be stored on a different computer device remotely located (e.g., a third party web server), and the physician may access the information using his/her own computer device. In this scenario, the three computer devices may be considered to operate together as a system. The physical and/or functional components of the computer system may be distributed, centralized, or arranged in any suitable manner. Communication between the different physical and/or functional components may be performed in any suitable manner. Moreover, the present invention encompasses all of the various ways in which operational work may be divided between different physical and/or functional components.

In some embodiments, the physical therapy information is received by the computer system from a first computer device, the database resides on a second computer device, and the physical therapy information is sent by the computer system to a third computer device. The computer devices may be separate. The first computer device may communicate with a second computer device, and the second computer device may communicate with a third computer device. In one aspect, a first computer device is programmed to receive physical therapy information from a subject, a database resides on a second computer device, and a third computer device receives the transmitted physical therapy information.

In other embodiments, a non-transitory computer-readable storage medium storing instructions is provided. The non-transitory computer readable medium, when executed by a computer system, causes the computer system to perform the steps of a computer-implemented method, the method comprising: receiving information associated with physical therapy from a subject undergoing physical therapy and botulinum toxin treatment for impaired voluntary motor ability; storing the physical therapy information in a database; and sending physical therapy information to a physician who has administered botulinum toxin treatment to the subject.

To assist in understanding the invention, certain embodiments are described in detail with reference to the accompanying drawings.

FIG. 1 shows a subject 10 being administered a dose of botulinum toxin by injection (e.g., through a syringe needle 12) into hyperactive muscle. The injection may be performed in any suitable clinical setting, such as in a hospital or clinic. The physician 30 determines which muscle, dose, etc. needs to be injected. Multiple injections may be performed if desired.

In conjunction with botulinum toxin treatment (e.g., following administration of an injection), physician 30 directs subject 10 to perform physical therapy activities and uses a computer software program to enter information associated with those physical therapy activities. Subject 10 is undergoing physical therapy as directed by physician 30. The physical therapy may be performed in any suitable manner, such as by a physical therapist, or under the supervision or guidance of a physical therapist, or directly by the subject 10 himself/herself (e.g., the subject 10 exercises himself, stretches, etc. at home), or a combination thereof.

Fig. 2 shows subject 10 entering information associated with a physical therapy into tablet computer 14. Installed on tablet computer 14 is an application that provides a user interface for subject 10 and receives information input by subject 10. Tablet computer 14 communicates with a host server computer 22 (e.g., operated by a vendor of software programs or a vendor of botulinum toxin or another third party) via a network link 20 (e.g., a connection through WiFi and then through the home internet). The information entered by subject 10 is transmitted to host server computer 22 and stored in a database resident therein.

In one embodiment, interaction of subject 10 with the software program alone is sufficient to enhance the efficacy of the treatment. For example, in a GSC strategy, the act of entering information associated with a physical therapy activity performed by subject 10 may give subject 10 a sense of success and encourage him/her to continue the physical therapy activity, thereby increasing the effectiveness of the treatment. In an alternative embodiment, the physician 30 reviews the physical therapy information, and the physician 30 can then use this information to determine a course of treatment, or make or suggest adjustments to an existing course of treatment.

Fig. 3 shows the physician 30 working on a personal computer 32, which personal computer 32 communicates with the host server computer 22 via a communication link 24 (e.g., through an office internet connection). Using personal computer 32, physician 30 can access the physical therapy information of subject 10 stored on host server computer 22 and view the information. In an alternative embodiment, subject 10 may bring tablet computer 14 to physician 30, who physician 30 then views the information directly on tablet computer 14.

Based on review of this information, physician 30 may perform any suitable action to improve clinical management of impaired voluntary motor ability of subject 10. For example, the physician may inform the subject 10 that he/she is happy to see the progress made by the subject 10 and encourage the continuation of physical therapy. In an alternative embodiment, a physician may use this information to make a decision regarding further treatment of the subject with botulinum toxin. For example, subject 10 may receive injections of botulinum toxin intermittently at regular intervals (e.g., every three months), and after reviewing the physical therapy information of subject 10, physician 30 may decide to adjust the botulinum toxin treatment, such as adjusting the mode of administration, the frequency or amount of each dose, or which muscle to select for administration of botulinum toxin.

Physician 30 may access and review the physical therapy information of subject 10 during an outpatient visit of subject 10 or in preparation for the next outpatient visit of subject 10. After reviewing the physical therapy information and making a decision to adjust botulinum toxin treatment, a doctor 30 (or another medical professional) may administer botulinum toxin to subject 10 based on the adjustments in pattern, dose, frequency, muscle selection, etc.

It is to be understood that the present invention is not limited to the embodiments, aspects or features described above, but encompasses any and all embodiments, aspects or features within the scope of the subjoined claims.

All of the above references are incorporated herein by reference in their entirety.

Claims (108)

1. A method for improving active locomotor ability of a subject, the method comprising:

administering to a subject in need thereof a first botulinum toxin treatment to a muscle affected by an impaired voluntary motor ability;

directing the subject to: (a) performing a physical therapy comprising a physical activity involving the affected muscle; and (b) recording information associated with the physical therapy;

designing a treatment regimen based at least in part on the physical therapy information of the subject; and

administering a second botulinum toxin treatment to the subject according to the treatment protocol, wherein the botulinum toxin treatment is sufficient to improve the subject's voluntary locomotor ability.

2. The method of claim 1, wherein the step of administering the botulinum toxin treatment comprises injecting botulinum toxin into the affected muscle.

3. The method of claim 1 or 2, wherein the step of administering the botulinum toxin treatment comprises injecting botulinum toxin into a neuromuscular junction.

4. The method of any of claims 1-3, wherein the physiotherapy information comprises a type of physical activity performed, a duration of the physical activity, a frequency of the physical activity, and/or a symptom related to the impaired voluntary motor capacity.

5. The method of any one of claims 1-4, wherein the physical therapy comprises stretching the affected muscle, exercising the affected muscle, training the affected muscle, performing an alternating motion of the affected muscle, heating or cooling the affected muscle, contracting or relaxing the affected muscle, and/or body positioning.

6. The method of any of claims 1-5, wherein the physical therapy information is received on a first computer device and accessed on a second computer device.

7. The method of any of claims 1-6, wherein recording the physical therapy information enhances improved voluntary locomotor capacity associated with the botulinum toxin treatment.

8. The method of any of claims 1-7, wherein the subject has had a stroke, and wherein the administration of the first botulinum toxin therapy occurs within three months of the stroke.

9. The method of any of claims 1-8, further comprising administering an initial botulinum toxin treatment prior to the development of impaired voluntary motor capacity prior to administering the first botulinum toxin treatment.

10. The method of claim 9, wherein the subject has had a stroke, and wherein the initial botulinum toxin treatment is administered within three months of the stroke.

11. The method of any of claims 1-10, wherein recording the physical therapy information comprises inputting the physical therapy information into a software program configured to receive the information.

12. The method of claim 11, wherein the software program operates on a computer device.

13. The method of claim 11 or 12, wherein the physical therapy information is stored in a database.

14. The method of any one of claims 1-13, wherein motivation of the subject is improved as a result of recording the physical therapy information.

15. The method of any one of claims 1-14, wherein the subject is more concerned with the physical therapy as a result of recording the physical therapy information.

16. The method of any of claims 1-15, wherein the improvement in active locomotor capacity is substantial.

17. The method of any one of claims 1-16, wherein the subject is regularly instructed by a physician.

18. The method of claim 17, wherein the physician selects and imparts the physical activity to the subject.

19. The method of claim 17 or 18, wherein the physician provides encouragement to the subject, which results in improved compliance with the physical therapy and contributes to improved voluntary locomotion ability of the subject.

20. The method of any one of claims 17-19, wherein the subject visits the physician two or more times over the course of a year.

21. The method of any one of claims 17-19, wherein the subject visits the physician three or more times over the course of a year.

22. The method of any one of claims 17-19, wherein the subject visits the physician four or more times over the course of a year.

23. The method of any one of claims 17-19, wherein the subject visits the physician five or more times over the course of a year.

24. The method of any one of claims 17-19, wherein the subject visits the physician six or more times over the course of a year.

25. The method of any one of claims 1-24, wherein the physical therapy is appropriate for a particular subject.

26. The method of any one of claims 1-25, wherein the subject is instructed to undergo physical therapy daily.

27. The method of any one of claims 1-26, wherein the subject is instructed to record the physical therapy information daily.

28. The method of any one of claims 1-27, wherein the subject performs the physical therapy daily.

29. The method of any one of claims 1-28, wherein the subject records the physical therapy information daily.

30. In a method for improving active locomotor ability of a subject, the method comprising:

administering to the subject in need of such treatment a first botulinum toxin treatment to a muscle affected by an impaired voluntary motor ability; and

instructing the subject to perform a physical therapy comprising physical activity involving the affected muscle;

wherein the improvement comprises:

instructing the subject to record information associated with the physical therapy;

reviewing recorded physical therapy information of the subject;

designing a treatment regimen based at least in part on the physical therapy information of the subject; and

administering a second botulinum toxin therapy to the subject according to the treatment protocol, wherein the botulinum toxin therapy is sufficient to treat the impaired voluntary locomotion capacity.

31. The method of claim 30, wherein the steps of administering the first botulinum toxin treatment and administering the second botulinum toxin treatment comprise injecting botulinum toxin into the affected muscle.

32. The method of claim 30 or 31, wherein the physiotherapy information comprises a type of physical activity performed, a duration of the physical activity, a frequency of the physical activity, and/or symptoms related to the impaired voluntary motor capacity.

33. The method of any one of claims 30-32, wherein the physical therapy comprises stretching the affected muscle, exercising the affected muscle, training the affected muscle, performing an alternating motion of the affected muscle, heating or cooling the affected muscle, contracting or relaxing the affected muscle, and/or body positioning.

34. The method of any of claims 30-33, wherein the physical therapy information is received on a first computer device and accessed on a second computer device.

35. The method of any one of claims 30-34, wherein instructing the subject to record the physical therapy information comprises instructing the subject to enter the physical therapy information into a software program configured to receive the information.

36. The method of claim 35, wherein the software program operates on a computer device.

37. The method of claim 35 or 36, wherein the physical therapy information is stored in a database.

38. The method of any one of claims 30-37, wherein motivation of the subject is improved as a result of recording the physical therapy information.

39. The method of any one of claims 30-38, wherein the subject is more concerned with the physical therapy as a result of recording the physical therapy information.

40. The method of any of claims 30-39, wherein the improvement in active locomotor capacity is substantial.

41. The method of any one of claims 30-40, wherein the subject is regularly instructed by a physician.

42. The method of claim 41, wherein said physician selects and imparts said physical activity to said subject.

43. The method of claim 41 or 42, wherein the physician provides encouragement to the subject, which results in improved compliance with the physical therapy and contributes to improved voluntary locomotion ability of the subject.

44. The method of any one of claims 41-43, wherein the subject visits the physician two or more times over the course of a year.

45. The method of any one of claims 41-43, wherein the subject visits the physician three or more times over the course of a year.

46. The method of any one of claims 41-43, wherein the subject visits the physician four or more times over the course of a year.

47. The method of any one of claims 41-43, wherein the subject visits the physician five or more times over the course of a year.

48. The method of any one of claims 41-43, wherein the subject visits the physician six or more times over the course of a year.

49. The method of any one of claims 30-48, wherein the physical therapy is appropriate for a particular subject.

50. The method of any one of claims 30-49, wherein the subject is instructed to undergo physical therapy daily.

51. The method of any one of claims 30-50, wherein the subject is instructed to record the physical therapy information daily.

52. The method of any one of claims 30-51, wherein the subject performs the physical therapy daily.

53. The method of any one of claims 30-52, wherein the subject records the physical therapy information daily.

54. In a method for improving active locomotor ability of a subject using a botulinum toxin, the improvement comprising:

determining an appropriate botulinum toxin treatment based on a physician's assessment of how the subject responds to a prescribed physical therapy regimen involving: (i) administering botulinum toxin to improve voluntary motor capacity of a muscle affected by impaired voluntary motor capacity; (ii) engaging in physical activity involving the affected muscles; and (iii) recording information associated with the physical therapy.

55. The method of claim 54, wherein the step of administering the botulinum toxin treatment comprises injecting botulinum toxin into the affected muscle.

56. The method of claim 54 or 55, wherein the physiotherapy information comprises a type of physical activity performed, a duration of the physical activity, a frequency of the physical activity, and/or a symptom related to the impaired voluntary motor capacity.

57. The method of any one of claims 54-56, wherein the physical therapy includes stretching the affected muscle, exercising the affected muscle, training the affected muscle, performing an alternating motion of the affected muscle, heating or cooling the affected muscle, contracting or relaxing the affected muscle, and/or body positioning.

58. The method of any of claims 54-57, wherein the physical therapy information is received on a first computer device and accessed on a second computer device.

59. The method of any of claims 54-58, wherein recording the physical therapy information comprises inputting the physical therapy information into a software program configured to receive the information.

60. The method of claim 59, wherein the software program operates on a computer device.

61. The method of claim 59 or 60, wherein the physical therapy information is stored in a database.

62. The method of any one of claims 54-61, wherein motivation of the subject is improved as a result of recording the physical therapy information.

63. The method of any one of claims 54-62, wherein the subject is more concerned with the physical therapy as a result of recording the physical therapy information.

64. The method of any of claims 54-63, wherein the improvement in active locomotor capacity is substantial.

65. The method of any one of claims 54-64, wherein the subject is regularly instructed by a physician.

66. The method of claim 65, wherein said physician selects and imparts said physical activity to said subject.

67. The method of claim 65 or 66, wherein the physician provides encouragement to the subject, which results in improved compliance with the physical therapy and contributes to improved voluntary locomotion ability of the subject.

68. The method of any one of claims 65-67, wherein the subject visits the physician two or more times over the course of a year.

69. The method of any one of claims 65-67, wherein the subject visits the physician three or more times over the course of a year.

70. The method of any one of claims 65-67, wherein the subject visits the physician four or more times over the course of a year.

71. The method of any one of claims 65-67, wherein the subject visits the physician five or more times over the course of a year.

72. The method of any one of claims 65-67, wherein the subject visits the physician six or more times over the course of a year.

73. The method of any one of claims 54-72, wherein the physical therapy is appropriate for a particular subject.

74. The method of any one of claims 54-73, wherein the subject is instructed to undergo physical therapy daily.

75. The method of any one of claims 54-74, wherein the subject is instructed to record the physical therapy information daily.

76. The method of any one of claims 54-75, wherein the subject performs the physical therapy daily.

77. The method of any one of claims 54-76, wherein the subject records the physical therapy information daily.

78. A method for improving active locomotor ability of a subject, the method comprising:

receiving a first botulinum toxin treatment to a muscle affected by an impaired voluntary motor ability;

performing a physical therapy comprising a physical activity involving the affected muscle;

recording information associated with the physical therapy;

receiving a second botulinum toxin treatment, wherein the second treatment is determined based at least in part on the recorded physical therapy information.

79. The method of claim 78, further comprising receiving a third botulinum toxin treatment, wherein the third treatment is determined, at least in part, with respect to information received by the software program.

80. The method of claim 78 or 79, wherein recording the physical therapy information enhances the improved voluntary locomotor capacity associated with the botulinum toxin treatment.

81. The method of any of claims 78-80, wherein the receiving of the first botulinum toxin treatment occurs within three months of a stroke.

82. The method of any of claims 78-81, further comprising receiving an initial botulinum toxin treatment prior to the development of impaired voluntary motor capacity prior to receiving the first botulinum toxin treatment.

83. The method of claim 82, wherein the initial botulinum toxin treatment is received within three months of stroke.

84. The method of any of claims 78-83, wherein recording the physical therapy information includes inputting the physical therapy information into a software program configured to receive the information.

85. The method of claim 84, wherein the software program operates on a computer device.

86. The method of claim 84 or 85, wherein the physical therapy information is stored in a database.

87. The method of any of claims 78-86, wherein motivation of the subject is improved as a result of recording the physical therapy information.

88. The method of any of claims 78-87, wherein the subject is more concerned with the physical therapy as a result of recording the physical therapy information.

89. The method of any of claims 78-88, where the improvement in active locomotor capacity is substantial.

90. The method of any one of claims 78-89, wherein the subject is regularly instructed by a physician.

91. The method of claim 90, wherein the physician selects and imparts the physical activity to the subject.

92. The method of claim 90 or 91, wherein the physician provides encouragement to the subject, which results in improved compliance with the physical therapy and contributes to improved voluntary locomotion ability of the subject.

93. The method of any one of claims 90-92, wherein the subject visits the physician two or more times over the course of a year.

94. The method of any one of claims 90-92, wherein the subject visits the physician three or more times over the course of a year.

95. The method of any one of claims 90-92, wherein the subject visits the physician four or more times over the course of a year.

96. The method of any one of claims 90-92, wherein the subject visits the physician five or more times over the course of a year.

97. The method of any one of claims 90-92, wherein the subject visits the physician six or more times over the course of a year.

98. The method of any of claims 78-97, wherein the physical therapy is appropriate for a particular subject.

99. The method of any of claims 78-98, wherein the subject is instructed to undergo physical therapy daily.

100. The method of any of claims 78-99, wherein the subject is instructed to record the physical therapy information daily.

101. The method of any of claims 78-100, wherein the subject performs the physical therapy daily.

102. The method of any of claims 78-101, wherein the subject records the physical therapy information daily.

103. A computer system programmed to perform the steps of a computer-implemented method, the method comprising:

receiving information associated with physical therapy and botulinum toxin treatment for impaired voluntary motor ability from a subject undergoing the physical therapy;

storing the physical therapy information in a database; and

transmitting the physical therapy information to a physician who has administered the botulinum toxin treatment to the subject.

104. The computer system of claim 103, wherein the physical therapy information is received by the computer system from a first computer device, the database resides on a second computer device that is part of the computer system, and the physical therapy information is sent by the computer system to a third computer device.

105. The computer system of claim 104, wherein the first computer device, second computer device, and third computer device are each separate computer devices.

106. The computer system of claim 103, wherein the computer system comprises:

a first computer device programmed to receive the physical therapy information from the subject;

a second computer device on which the database resides; and

a third computer device that receives the transmitted physical therapy information.

107. The computer system of claim 106, wherein the first, second, and third computer devices are each separate computer devices;

the first computer device communicating with the second computer device; and

the third computer device is in communication with the second computer device.

108. A non-transitory computer readable storage medium storing instructions that, when executed by a computer system, cause the computer system to perform the steps of a computer-implemented method, the method comprising:

receiving information associated with physical therapy and botulinum toxin treatment for impaired voluntary motor ability from a subject undergoing the physical therapy;

storing the physical therapy information in a database; and

transmitting the physical therapy information to a physician who has administered the botulinum toxin treatment to the subject.