ERK inhibitors for use in treating spinal muscular atrophy
View Patent ↗The present invention relates to a method for treating spinal muscular atrophy and other related neuromuscular disorders in a subject in need thereof, said method comprising administering a therapeutically effective amount of an ERK inhibitor, such as Selumetinib to said subject.
1. A method of treating spinal muscular atrophy in a subject in need thereof comprising:
administering to the subject an effective amount of an ERK inhibitor;
wherein said ERK inhibitor is a selective MEK inhibitor; and
wherein said spinal muscular atrophy is associated with deficiency in a Survival-Motor-Neuron gene, said deficiency resulting in loss of motor function.
2. The method according to claim 1 , wherein said deficiency resulting in loss of motor function is a genetic mutation in Survival-Motor-Neuron 1 gene.
3. The method according to claim 1 , wherein said ERK inhibitor is a MEK½ inhibitor.
4. The method according to claim 3 , wherein said MEK½ inhibitor is selected from selumetinib, U0126, PD98059, PD0325901, AZD8330, CI-1040 and PD318088.
5. The method according to claim 3 , wherein said ERK inhibitor is selected from the group consisting of selumetinib and its derivatives and pharmaceutically acceptable salts thereof.
6. The method according to claim 1 , wherein said ERK inhibitor is selected from the group consisting of nucleic acid molecule, siRNA, shRNA and anti-sense oligonucleotide; said nucleic acid molecule reducing the expression of MEK1, MEK2, ERK1 or ERK2.
7. The method according to claim 1 , wherein said ERK inhibitor is administered orally to a subject in an amount effective to treat spinal muscular atrophy.
8. A method of treating spinal muscular atrophy in a subject in need thereof comprising:
administering to the subject an effective amount of at least one agent selected from selumetinib, U0126, PD98059, PD0325901, AZD8330, CI-1040 and PD318088.
9. The method of claim 3 wherein, the ERK inhibitor has an IC50 of at least 1μM, or less.
10. The method according to claim 3 , wherein said ERK inhibitor is selected from the group consisting of U0126 and its derivatives and pharmaceutically acceptable salts thereof.
11. The method according to claim 8 , comprising administering to the subject an effective amount of U0126.
12. The method according to claim 8 , comprising administering to the subject an effective amount of selumetinib.