Abstract: One aspect of the invention provides a method of ovarian protection by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). Ovarian protection can be an induced arrest of folliculogenesis to preserve fertility. In some embodiments, ovarian protection is oncoprotection, the protection of the ovarian function during a cytotoxic treatment, e.g., chemotherapy. Another aspect of the invention relates to a method of treating PCOS, the method comprising administering to a female subject a composition comprising recombinant MIS protein.

Abstract: One aspect of the invention provides a method of ovarian protection by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). Ovarian protection can be an induced arrest of folliculogenesis to preserve fertility. In some embodiments, ovarian protection is oncoprotection, the protection of the ovarian function during a cytotoxic treatment, e.g., chemotherapy. Another aspect of the invention relates to a method of treating PCOS, the method comprising administering to a female subject a composition comprising recombinant MIS protein.

Abstract: The present invention relates to modified recombinant human MIS protein which has improved cleavage and increased bioactivity and increased potency as compared to wild-type human MIS protein. Other aspects of the invention relate to methods to prevent and treat cancers, such as cancers that express the MIS receptor type II (MISRII) by administering to a subject a composition comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to lower plasma androgen levels in a subject, and/or for the treatment of a subject with a disease characterized by excess androgen. Another aspect provides pharmaceutical compositions and kits and methods for use comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent with the recombinant MIS protein that lowers the effective dose of the chemotherapeutic agent.

Abstract: One aspect of the invention provides a method of contraception by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). The MIS can be produced endogenously in the subject by a vector, where the vector comprises a polynucleotide encoding a recombinant MIS protein. In some embodiments, the contraception is permanent and only requires administration of the composition once. Another aspect of the invention relates to a method of preserving an ovarian reserve, the method comprising administering to a female subject a composition comprising MIS or an inducible vector that comprises a polynucleotide encoding a recombinant MIS protein.

Abstract: The present invention relates to modified recombinant human MIS protein which has improved cleavage and increased bioactivity and increased potency as compared to wild-type human MIS protein. Other aspects of the invention relate to methods to prevent and treat cancers, such as cancers that express the MIS receptor type II (MISRII) by administering to a subject a composition comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to lower plasma androgen levels in a subject, and/or for the treatment of a subject with a disease characterized by excess androgen. Another aspect provides pharmaceutical compositions and kits and methods for use comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent with the recombinant MIS protein that lowers the effective dose of the chemotherapeutic agent.

Abstract: One aspect of the invention provides a method of contraception by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). The MIS can be produced endogenously in the subject by a vector, where the vector comprises a polynucletide encoding a recombinant MIS protein. In some embodiments, the contraception is permanent and only requires administration of the composition once. Another aspect of the invention relates to a method of preserving an ovarian reserve, the method comprising administering to a female subject a composition comprising MIS or an inducible vector that comprises a polynucleotide encoding a recombinant MIS protein.

Abstract: One aspect of the invention provides a method of ovarian protection by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). Ovarian protection can be an induced arrest of folliculogenesis to preserve fertility. In some embodiments, ovarian protection is oncoprotection, the protection of the ovarian function during a cytotoxic treatment, e.g., chemotherapy. Another aspect of the invention relates to a method of treating PCOS, the method comprising administering to a female subject a composition comprising recombinant MIS protein.

Abstract: The present invention relates to methods to treat a neurodegenerative disease or disorder, e.g., a motor neuron disease in a subject, whereby the subject is administered a recombinant human Mullerian Inhibiting Substance (MIS) protein as disclosed herein, wherein the recombinant human MIS protein comprises a modified Kex cleavage site for increased cleavage. The recombinant human MIS protein can be produced from a pre-proprotein comprising a non-MIS leader sequence or a functional fragment thereof in place of the MIS leader sequence.

Abstract: The present invention relates to methods to treat a neurodegenerative disease or disorder, e.g., a motor neuron disease in a subject, whereby the subject is administered a recombinant human Mullerian Inhibiting Substance (MIS) protein as disclosed herein, wherein the recombinant human MIS protein comprises a modified Kex cleavage site for increased cleavage. The recombinant human MIS protein can be produced from a pre-proprotein comprising a non-MIS leader sequence or a functional fragment thereof in place of the MIS leader sequence.

Abstract: One aspect of the invention provides a method of contraception by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). The MIS can be produced endogenously in the subject by a vector, where the vector for comprises a polynucletide encoding a recombinant MIS protein. In some embodiments, the contraception is permanent and only requires administration of the composition once. Another aspect of the invention relates to a method of preserving an ovarian reserve, the method comprising administering to a female subject a composition comprising MIS or an inducible vector that comprises a polynucleotide encoding a recombinant MIS protein.

Abstract: The present invention relates to a N1-methyl-pyrazoloanthrone, e.g., a N1-methyl 1,9-pyrazoloanthrone or functional derivatives or analogues thereof to inhibit at least one kinase of the CK1 family (e.g., CSNK1A1, CSNK1B, CSNK1G1, CSNK1G2, CSNK1G3, CSNK1D, CSNK1E) and/or ARK5/NUAK1 in a cell. Another aspect relates to administration of N1-methyl-pyrazoloanthrone, e.g., a N1-methyl 1,9-pyrazoloanthrone or a functional derivative thereof in a method to treat cancer, e.g., a cancer with increased expression and/or a genetic alteration in at least one member of the CK1 family and/or ARK5/NUAK. Another aspect of the present invention relates to methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent in combination with a N1-methyl-pyrazoloanthrone, e.g., a N1-methyl 1,9-pyrazoloanthrone or a functional derivative or analogue thereof.

Abstract: The present invention relates to methods to treat a neurodegenerative disease or disorder, e.g., a motor neuron disease in a subject, whereby the subject is administered a recombinant human Mullerian Inhibiting Substance (MIS) protein as disclosed herein, wherein the recombinant human MIS protein comprises a modified Kex cleavage site for increased cleavage. The recombinant human MIS protein can be produced from a pre-proprotein comprising a non-MIS leader sequence or a functional fragment thereof in place of the MIS leader sequence.

Abstract: The present invention relates to modified recombinant human MIS protein which has improved cleavage and increased bioactivity and increased potency as compared to wild-type human MIS protein. Other aspects of the invention relate to methods to prevent and treat cancers, such as cancers that express the MIS receptor type II (MISRII) by administering to a subject a composition comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to lower plasma androgen levels in a subject, and/or for the treatment of a subject with a disease characterized by excess androgen. Another aspect provides pharmaceutical compositions and kits and methods for use comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent with the recombinant MIS protein that lowers the effective dose of the chemotherapeutic agent.