Treatment of spinal muscular atrophy
AssigneesUniversity of Pittsburgh—Of the Commonwealth System of Higher Education, Genentech, Inc.
InventorsMarco CAPOGROSSO, Mikael John Lars ELIASSON, Genis PRAT ORTEGA
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Abstract
Disclosed herein are methods for treating spinal muscular atrophy in a subject. Particular methods comprise applying a therapeutically effective amount of an electrical stimulus to sensory neurons innervating a body region of the subject with a motor impairment due to the spinal muscle atrophy, wherein application of the electrical stimulus treats the motor impairment due to spinal muscular atrophy in the subject.
Claims134
A method for treating spinal muscular atrophy (SMA) in a subject, comprising:
- applying a therapeutically effective amount of an electrical stimulus to sensory neurons innervating a body region of the subject with a motor impairment due to SMA, wherein the electrical stimulus is applied with one or more electrodes controlled by a neurostimulator, and wherein application of the electrical stimulus treats the motor impairment due to SMA in the subject.
The method of any one of the prior claims, wherein the electrical stimulus comprises a stimulation pattern of a series of 2 to 5 pulses separated by inter-pulse intervals of about 3 ms to about 10 ms and wherein the series is repeated at a frequency of about 10 Hz to about 100 Hz.
The method of any one of the prior claims, wherein the electrical stimulus is applied for at least 2 hours/day over a period of at least 6 months.
The method of any one of the prior claims, wherein the one or more electrodes are contained within an array of independently controllable electrodes implanted in the subject.
The method of any one of the prior claims, wherein the one or more electrodes are implanted epidurally at the spinal cord of the subject.
The method of any one of the prior claims, wherein the body region of the subject is selected from at least one of lower back, hip, leg, ankle, and foot;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the T11-S1 nerve roots.
The method of any one of the prior claims, wherein the body region of the subject is selected from at least one of upper arm, shoulder, arm, hand, and respiratory muscles;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the C3-T2 nerve roots.
The method of any one of the prior claims, wherein the body region of the subject is selected from at least one of the chest, chest wall, abdomen, upper back, and middle back;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the T3-T10 nerve roots.
The method of any one of the prior claims, wherein the neurostimulator is an external or implanted pulse generator.
The method of any one of the prior claims, further comprising implanting the neurostimulator in the subject.
The method of any one of the prior claims, further comprising selecting the subject with SMA for treatment.
The method of any one of the prior claims, wherein the motor impairment comprises partial or complete paralysis, loss of dexterity, loss of muscle strength, and/or uncontrollable muscle tone.
The method of any one of the prior claims, wherein the locations of the one or more electrodes are chosen based on the body region of the subject with the motor impairment due to SMA.
The method of any one of the prior claims, wherein at least one of the one or more electrodes is placed transcutaneously.
The method of any one of the prior claims, wherein at least one of the one or more electrodes is implanted.
A method of stimulating one or more motoneurons impaired by SMA, said method comprising applying an electrical stimulus to at least one of said motoneurons, wherein said motoneurons innervate a body region of a subject with a motor impairment due to SMA.
A method for treating SMA in a subject, comprising applying a therapeutically effective amount of an electrical stimulus to sensory neurons innervating a body region of the subject with a motor impairment due to SMA.
A method of increasing firing rate of motoneurons impaired by SMA in a subject, comprising applying a therapeutically effective amount of an electrical stimulus to sensory neurons innervating a body region of the subject to increase the motoneuron firing rate of the subject.
A method of increasing excitability of motoneurons impaired by SMA in a subject to a sensory afferent input, comprising applying a therapeutically effective amount of an electrical stimulus to sensory neurons innervating a body region of the subject to increase the motoneuron excitability of the subject.
A therapeutically effective amount of an electrical stimulus to sensory neurons innervating a body region of the subject with a motor impairment due to SMA for treating SMA in a subject, wherein the electrical stimulus is to be applied with one or more electrodes controlled by a neurostimulator, and wherein application of the electrical stimulus treats the motor impairment due to SMA in the subject.
The electrical stimulus for use of any one of the prior claims, wherein the electrical stimulus comprises a stimulation pattern of a series of 2 to 5 pulses separated by inter-pulse intervals of about 3 ms to about 10 ms and wherein the series is repeated at a frequency of about 10 Hz to about 100 Hz.
The electrical stimulus for use of any one of the prior claims, wherein the electrical stimulus is applied for at least 2 hours/day over a period of at least 6 months.
The electrical stimulus for use of any one of the prior claims, wherein the one or more electrodes are contained within an array of independently controllable electrodes implanted in the subject.
The electrical stimulus for use of any one of the prior claims, wherein the one or more electrodes are implanted epidurally at the spinal cord of the subject.
The electrical stimulus for use of any one of the prior claims, wherein the body region of the subject is selected from at least one of lower back, hip, leg, ankle, and foot;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the T11-S1 nerve roots.
The electrical stimulus for use of any one of the prior claims, wherein the body region of the subject is selected from at least one of upper arm, shoulder, arm, hand, and respiratory muscles;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the C3-T2 nerve roots.
The electrical stimulus for use of any one of the prior claims, wherein the body region of the subject is selected from at least one of the chest, chest wall, abdomen, upper back, and middle back;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the T3-T10 nerve roots.
The electrical stimulus for use of any one of the prior claims, wherein the neurostimulator is an external or implanted pulse generator.
The electrical stimulus for use of any one of the prior claims, wherein the neurostimulator is implanted in the subject.
The electrical stimulus for use of any one of the prior claims, wherein the subject with SMA is selected for treatment.
The electrical stimulus for use of any one of the prior claims, wherein the motor impairment comprises partial or complete paralysis, loss of dexterity, loss of muscle strength, and/or uncontrollable muscle tone.
The electrical stimulus for use of any one of the prior claims, wherein the locations of the one or more electrodes are chosen based on the body region of the subject with the motor impairment due to SMA.
The electrical stimulus for use of any one of the prior claims, wherein at least one of the one or more electrodes is placed transcutaneously.
The electrical stimulus for use of any one of the prior claims, wherein at least one of the one or more electrodes is implanted.
Use of one or more electrodes controlled by a neurostimulator in the manufacture of a medicament for treating SMA in a subject, wherein the one or more electrodes controlled by the neurostimulator are configured to apply a therapeutically effective amount of an electrical stimulus to sensory neurons innervating a body region of the subject with a motor impairment due to SMA.
The use of any one of the prior claims, wherein the electrical stimulus comprises a stimulation pattern of a series of 2 to 5 pulses separated by inter-pulse intervals of about 3 ms to about 10 ms and wherein the series is repeated at a frequency of about 10 Hz to about 100 Hz.
The use of any one of the prior claims, wherein the electrical stimulus is applied for at least 2 hours/day over a period of at least 6 months.
The use of any one of the prior claims, wherein the one or more electrodes are contained within an array of independently controllable electrodes implanted in the subject.
The use of any one of the prior claims, wherein the one or more electrodes are implanted epidurally at the spinal cord of the subject.
The use of any one of the prior claims, wherein the body region of the subject is selected from at least one of lower back, hip, leg, ankle, and foot;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the T11-S1 nerve roots.
The use of any one of the prior claims, wherein the body region of the subject is selected from at least one of upper arm, shoulder, arm, hand, and respiratory muscles;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the C3-T2 nerve roots.
The use of any one of the prior claims, wherein the body region of the subject is selected from at least one of the chest, chest wall, abdomen, upper back, and middle back;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the T3-T10 nerve roots.
The use of any one of the prior claims, wherein the neurostimulator is an external or implanted pulse generator.
The use of any one of the prior claims, wherein the neurostimulator is implanted in the subject.
The use of any one of the prior claims, wherein the subject with SMA is selected for treatment.
The use of any one of the prior claims, wherein the motor impairment comprises partial or complete paralysis, loss of dexterity, loss of muscle strength, and/or uncontrollable muscle tone.
The use of any one of the prior claims, wherein the locations of the one or more electrodes are chosen based on the body region of the subject with the motor impairment due to SMA.
The use of any one of the prior claims, wherein at least one of the one or more electrodes is placed transcutaneously.
The use of any one of the prior claims, wherein at least one of the one or more electrodes is implanted.
Use of one or more electrodes controlled by a neurostimulator in the manufacture of a medicament for treating SMA in a subject, wherein an electrical stimulus is to be applied using the one or more electrodes controlled by the neurostimulator to sensory neurons innervating a body region of the subject with a motor impairment due to SMA.
The use of any one of the prior claims, wherein the electrical stimulus comprises a stimulation pattern of a series of 2 to 5 pulses separated by inter-pulse intervals of about 3 ms to about 10 ms and wherein the series is repeated at a frequency of about 10 Hz to about 100 Hz.
The use of any one of the prior claims, wherein the electrical stimulus is applied for at least 2 hours/day over a period of at least 6 months.
The use of any one of the prior claims, wherein the one or more electrodes are contained within an array of independently controllable electrodes implanted in the subject.
The use of any one of the prior claims, wherein the one or more electrodes are implanted epidurally at the spinal cord of the subject.
The use of any one of the prior claims, wherein the body region of the subject is selected from at least one of lower back, hip, leg, ankle, and foot;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the T11-S1 nerve roots.
The use of any one of the prior claims, wherein the body region of the subject is selected from at least one of upper arm, shoulder, arm, hand, and respiratory muscles;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the C3-T2 nerve roots.
The use of any one of the prior claims, wherein the body region of the subject is selected from at least one of the chest, chest wall, abdomen, upper back, and middle back;
- and the one or more electrodes are implanted at the dorsolateral aspect of the spinal cord and span one or more of the T3-T10 nerve roots.
The use of any one of the prior claims, wherein the neurostimulator is an external or implanted pulse generator.
The use of any one of the prior claims, wherein the neurostimulator is implanted in the subject.
The use of any one of the prior claims, wherein the subject with SMA is selected for treatment.
The use of any one of the prior claims, wherein the motor impairment comprises partial or complete paralysis, loss of dexterity, loss of muscle strength, and/or uncontrollable muscle tone.
The use of any one of the prior claims, wherein the locations of the one or more electrodes are chosen based on the body region of the subject with the motor impairment due to SMA.
The use of any one of the prior claims, wherein at least one of the one or more electrodes is placed transcutaneously.
The use of any one of the prior claims, wherein at least one of the one or more electrodes is implanted.
Dependencies are inferred from the claim text.