# US 2023/0273221 A1 · Method relating to myostatin pathway inhibition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0273221 A1 - Document ID: US20230273221A1 - Status: Published application - Kind: A1 - Application number: 18/312,879 - Filed: 2023-05-05 - Published: 2023-08-31 - Earliest claimed: 2017-03-10 - Assignees: UCL Business PLC - Applicants: UCL Business Ltd. - Inventors: Thomas Voit; Julie Dumonceaux; Virginie Mariot - Web page: https://patentgrep.com/patent/US20230273221A1 ## CPC - G01N 33/6887: {from muscle, cartilage or connective tissue} - A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants} - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - G01N 33/4833: {of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735)} - G01N 33/74: involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors} - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention provides a method for determining whether a patient will respond to treatment with a myostatin pathway inhibitor, the method comprising: (a) determining a level of myostatin and/or activin type II receptor (ActRII) and/or follistatin in at least one muscle biopsy obtained from a treatment target muscle in a subject having or suspected of having muscle atrophy or a muscle wasting condition; and (b) determining a level of myostatin and/or follistatin in a systemic sample obtained from the patient, wherein if: (i) the level of myostatin in the systemic sample is higher than a threshold and/or if the level of follistatin in the sample is lower than a threshold; and (ii) the level of myostatin and/or ActRII receptor in the at least one biopsy sample is higher than a threshold level and/or if the level of follistatin in the at least one biopsy sample is lower than a threshold level, the patient will respond to treatment. ## Claims ### Claim 1 A method for treating muscle atrophy or a muscle wasting condition to a subject in need thereof, the method comprising: administering a dystrophin, an MTM1 gene, or pathology correcting therapy, and a myostatin pathway inhibitor to the subject, thereby treating the muscle atrophy or the muscle wasting condition. ### Claim 2 (depends on 1) The method according to claim 1, wherein the myostatin pathway inhibitor is a myostatin antagonist or an ActRII antagonist. ### Claim 3 (depends on 2) The method according to claim 2, wherein the myostatin antagonist is an anti-myostatin antibody, a myostatin decoy, a follistatin, or a follistatin analogue. ### Claim 4 (depends on 2) The method according to claim 2, where the ActRII antagonist is an anti-ActRII antibody, an ActRII decoy, or an inhibitor of an effector downstream of the ActRII. ### Claim 5 (depends on 1) The method according to claim 1, wherein the muscle atrophy or muscle wasting condition is a muscle dystrophy such as: Becker Muscular Dystrophy (BMD), Duchenne Muscular Dystrophy (DMD), Facioscapulohumeral Dystrophy (FSHD), Limb Girdle Muscular Dystrophy (LGMD), or Congenital Muscular Dystrophy (CMD); a central or spinal muscular atrophy such as: Amyotrophic Lateral Sclerosis (ALS) or spinal muscular atrophy; a neurogenic muscular atrophy such as: Charcot-Marie-Tooth peripheral neuropathy; a congenital myopathy such as: Myotubular myopathy; or an ‘idiopathic’ muscle wasting condition such as: Inclusion Body Myositis (IBM) or age-related sarcopenia. ### Claim 6 (depends on 1) The method according to claim 1, comprising administering to the subject a vector comprising the MTM1 gene. ### Claim 7 (depends on 6) The method according to claim 6, wherein the viral vector is a retrovirus vector, an adenovirus vector, a lentivirus vector, a herpes simplex virus vector, or an adeno-associated virus vector. ### Claim 8 (depends on 1) The method according to claim 1, wherein the MTM1 gene and myostatin pathway inhibitor are administered separately, simultaneously or sequentially. ### Claim 9 (depends on 1) The method according to claim 1, wherein the MTM1 gene is administered prior to the myostatin pathway inhibitor. ### Claim 10 A method for improving or monitoring dystrophin or MTM1 gene or pathology correcting therapy, the method comprising determining a level of myostatin and/or ActRII and/or follistatin in a sample obtained from a subject. ### Claim 11 (depends on 10) The method according to claim 10, wherein a) determining a level of myostatin and/or ActRII and/or follistatin comprises measuring myostatin and/or ActRII and/or follistatin protein; or b) determining a level of myostatin and/or ActRII and/or follistatin comprises measuring myostatin and/or ActRII and/or follistatin mRNA. ### Claim 12 (depends on 10) The method according to claim 10, wherein the myostatin is measured in a pro-peptide or mature protein form. ### Claim 13 (depends on 10) The method according to claim 10, wherein a) the sample is a bodily fluid sample such as: a whole blood sample, a serum sample, a plasma sample or a urine sample; or b) a biopsy sample such as: a muscle biopsy, including a skeletal muscle biopsy sample. ### Claim 14 (depends on 10) The method according to claim 10, further comprising comparing the level of myostatin and/or follistatin to a threshold. ### Claim 15 (depends on 14) The method according to claim 14, wherein if the level of myostatin is below the threshold and/or if the level of follistatin is above the threshold, at least one further round of gene or pathology correcting therapy is administered to the subject. ### Claim 16 A method for treating muscle atrophy or a muscle wasting condition, the method comprising administering a dystrophin, MTM1 gene, or pathology correcting therapy to a subject having a myostatin and/or ActRII level lower than a threshold level. ### Claim 17 (depends on 16) The method according to claim 16, wherein the subject has at least one skeletal muscle that does not express ActRII. ### Claim 18 A method for determining anabolic capacity of the skeletal muscle system of a subject, the method comprising: (a) determining a level of myostatin and/or follistatin in a systemic sample obtained from the subject; and/or (b) determining a level of myostatin and/or ActRII and/or follistatin in at least one muscle biopsy obtained from the subject; wherein if (i) the level of myostatin in the systemic sample is lower than a threshold and/or if the level of follistatin in the systemic sample is higher than a threshold; and/or (ii) the level of myostatin and/or ActRII receptor in the at least one muscle biopsy sample is lower than a threshold level and/or if the level of follistatin in the at least one muscle biopsy sample is higher than a threshold level, the anabolic capacity of the skeletal muscle system is compromised, indicating the existence of a muscle wasting process in the subject. ### Claim 19 (depends on 18) The method according to claim 18, further comprising comparing one or more of the levels of myostatin, ActRII receptor and/or follistatin to a respective threshold to determine the activity of the muscle wasting process. ### Claim 20 (depends on 18) The method according to claim 18, further comprising treating the subject with a dystrophin, MTM1 gene or pathology correcting therapy, and/or a myostatin pathway inhibitor. ### Claim 21 A method for determining whether a patient having or suspected of having spinal muscular atrophy (SMA) will respond to treatment, the method comprising: determining a level of myostatin and/or follistatin and/or GDF11 in a systemic sample obtained from the patient; wherein a level of GDF11 above a threshold is associated with SMA; and wherein if the level of myostatin is higher than a threshold and/or if the level of follistatin in the sample is lower than a threshold, the patient will respond to treatment. ### Claim 22 (depends on 22) The method according to claim 22, wherein the systemic sample is a bodily fluid sample such as: a whole blood sample, a serum sample, a plasma sample or a urine sample. ### Claim 23 (depends on 21) The method according to claim 21, further comprising administering a treatment for SMA to a patient determined to respond to the treatment.