Compositions for treating muscular dystrophy
View Patent ↗Improved compositions and methods for treating muscular dystrophy by administering antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping are described.
1. A method for treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient eteplirsen at a dose of about 30 mg/kg weekly for more than 120 weeks, such that disease progression in the patient is delayed, thereby treating the patient.
2. The method according to claim 1 , wherein the patient is a pediatric patient.
3. The method according to claim 1 , wherein the patient is administered an oral corticosteroid for at least 24 weeks prior to the first dose of eteplirsen.
4. A method for reducing the loss of ambulation in a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient eteplirsen at a dose of about 30 mg/kg weekly for more than 120 weeks, thereby reducing the loss of ambulation relative to baseline, in the patient.
5. The method according to claim 4 , wherein the patient is a pediatric patient.
6. The method according to claim 4 , wherein the patient is administered an oral corticosteroid for at least 24 weeks prior to the first dose of eteplirsen.
7. A method for restoring an mRNA reading frame to induce dystrophin protein production in a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient eteplirsen at a dose of about 30 mg/kg weekly for more than 120 weeks, thereby restoring the mRNA reading frame to induce dystrophin protein production in the patient.
8. The method according to claim 7 , wherein the patient is a pediatric patient.
9. The method according to claim 7 , wherein the patient is administered an oral corticosteroid for at least 24 weeks prior to the first dose of eteplirsen.
10. The method of claim 4 , wherein the dystrophin protein production is measured by reverse transcription polymerase chain reaction (RT-PCR), Western blot analysis, or immunohistochemical detection.
11. The method of claim 4 , wherein ambulation is measured using the North Star Ambulatory Assessment.
12. A method for treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient eteplirsen at a dose of about 30 mg/kg weekly for more than 120 weeks, such that disease progression in the patient is delayed as measured by the 6 Minute Walk Test (6MWT), thereby treating the patient.
13. A method for reducing the loss of ambulation in a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient eteplirsen at a dose of about 30 mg/kg weekly for more than 120 weeks, thereby reducing the loss of ambulation relative to baseline in the patient as measured by the 6 Minute Walk Test (6MWT).
14. The method of claim 13 , wherein the patient loses less than 5% ambulation, relative to baseline, as measured by the 6 Minute Walk Test (6MWT) by 120 weeks.
15. The method of claim 13 , wherein the patient loses no greater than 13.9 meters walking distance relative to baseline, as measured by the 6 Minute Walk Test (6MWT) by 120 weeks.
16. The method of claim 13 , wherein the patient maintains ambulation for more than 1.5 years following treatment.
17. A method for reducing loss of pulmonary function in a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient eteplirsen at a dose of 30 mg/kg weekly for more than 120 weeks, thereby reducing the loss of pulmonary function in the patient relative to baseline.
18. The method of claim 17 , wherein pulmonary function is measured as Maximum Inspiratory Pressure (MIP).
19. The method of claim 17 , wherein respiratory muscle function in the patient improves at least 14.6% relative to baseline pulmonary function as measured as Maximum Inspiratory Pressure (MIP).
20. The method of claim 17 , wherein pulmonary function is measured as Maximum Expiratory Pressure (MEP).
21. The method of claim 17 , wherein respiratory muscle function in the patient improves at least 15% relative to baseline pulmonary function as measured as Maximum Expiratory Pressure (MEP).
22. The method of claim 17 , wherein pulmonary function is measured as Forced Vital Capacity (FVC).
23. The method of claim 1 , wherein the patient is 7 years of age or older.
24. The method of claim 1 , further comprising administering to the patient a corticosteroid.
25. The method of claim 24 , wherein the corticosteroid is Betamethasone, Budesonide, Cortisone, Dexamethasone, Hydrocortisone, Methylprednisolone, Prednisolone, or Prednisone.
26. The method of claim 24 , wherein the corticosteroid is administered prior to, in conjunction with, or subsequent to administration of eteplirsen.
27. The method of claim 1 , further comprising confirming that the patient has a mutation in the DMD gene that is amenable to exon 51 skipping.
28. A method for treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient eteplirsen at a dose of about 30 mg/kg weekly for more than 120 weeks to thereby treat DMD, wherein by 120 weeks of treatment respiratory muscle function in the patient improves at least 14.6% relative to baseline pulmonary function as measured as Maximum Inspiratory Pressure (MIP).
29. A method for treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient eteplirsen at a dose of about 30 mg/kg weekly for more than 120 weeks to thereby treat DMD, wherein by 120 weeks of treatment respiratory muscle function in the patient improves at least 15% relative to baseline pulmonary function as measured as Maximum Expiratory Pressure (MEP).