SIRNA-based therapy of Fibrodyplasia Ossificans Progressiva (FOP)
View Patent ↗This invention is directed to mutated Activin A type I receptor proteins (ACVR1) and isolated nucleic acids encoding same. The invention also relates to compositions and methods for siRNA-based regulation of mutated ACVR1 expression in the treatment of Fibrodysplasia Ossificans Progressiva (FOP).
1. A method of treating Fibrodysplasia Ossificans Progressiva (FOP) in a subject, comprising the step of administering to said subject a therapeutically effective amount of a siRNA specific against a nucleic acid encoding a mutated Activin A type I receptor (ACVR1) represented by SEQ ID NO: 21 relative to a nucleic acid encoding wild-type Activin A type I receptor protein (ACVR1) as set forth in SEQ ID NO: 26, wherein said siRNA has a passenger strand selected from SEQ ID NO: 56 or SEQ ID NO: 57.
2. The method of claim 1 , whereby treating comprises inhibiting, delaying onset or preventing.
3. The method of claim 1 , whereby treating comprises reducing the incidence of, alleviating symptoms or both.
4. The method of claim 1 , whereby the Fibrodysplasia Ossificans Progressiva (FOP) is inherited Fibrodysplasia Ossificans Progressiva (FOP).
5. The method of claim 1 , whereby the Fibrodysplasia Ossificans Progressiva (FOP) is sporadic Fibrodysplasia Ossificans Progressiva (FOP).
6. A method of treating a pathology associated with heterotopic ossification in a subject, comprising the step of administering to said subject a therapeutically effective amount of a siRNA specific against a nucleic acid encoding a mutated Activin A type I receptor (ACVR1) represented by SEQ ID NO: 21 relative to a nucleic acid encoding wild-type Activin A type I receptor protein (ACVR1) as set forth in SEQ ID NO: 26, wherein said siRNA has a passenger strand selected from SEQ ID NO: 56 or SEQ ID NO: 57.
7. The method of claim 6 , whereby the pathology associated with heterotopic ossification is hip replacement surgery, valvular heart disease, closed head trauma, spinal cord injuries, sports injuries, blast injuries, or a combination thereof.
8. The method of claim 7 , further comprising administering to said subject a therapeutically effective amount of a BMP signal-transduction inhibitor.
9. An allele-specific siRNA, comprising a siRNA specific against a nucleic acid encoding a mutated Activin A type I receptor (ACVR1) represented by SEQ ID NO: 21 relative to a nucleic acid encoding wild-type Activin A type I receptor protein (ACVR1) as set forth in SEQ ID NO: 26 wherein said siRNA has a passenger strand selected from SEQ ID NO: 56 or SEQ ID NO: 57.