Methods for diagnosing and treating myhre syndrome

Patent metadata

Field	Value
Publication number	US-2016369348-A1
Application number	US-201615256809-A
Country	US
Kind code	A1
Filing date	Sep 6, 2016
Priority date	Jul 27, 2011
Publication date	Dec 22, 2016
Grant date	—

Abstract

The present invention relates to methods for diagnosing and treating Myhre Syndrome. The invention provides a method for diagnosing or predicting Myhre Syndrome, or a risk of Myhre Syndrome, in a subject, which method comprises detecting a mutation in SMAD4 gene, as compared to a control population, wherein the presence of said mutation is indicative of Myhre Syndrome or of a risk of Myhre Syndrome. The present invention also relates to an inhibitor of the SMAD4-mediated TGβ/BMP signalling pathway for use in the treatment of Myhre Syndrome.

First claim

1 - 8 . (canceled)

9 . The method of claim 13 , wherein said inhibitor of the SMAD4-mediated TGFβ/BMP signalling pathway is selected from the group consisting of inhibitors of TGFβ expression, inhibitors of BMP expression, inhibitors of SMAD4 expression, inhibitors of SMAD2 expression, inhibitors of SMAD3 expression, inhibitors of SMAD5 expression and inhibitors of SMAD8 expression.

10 . The method of claim 13 , wherein said inhibitor of the SMAD4-mediated TGFβ/BMP signalling pathway is a TGFβ antagonist.

11 . A method for diagnosing or predicting Myhre Syndrome, or a risk of Myhre Syndrome, in a subject, which method comprises
detecting, in a sample from the subject, a mutation in a SMAD4 gene by: i) isolating nucleic acid encoding the SMAD4 gene from the sample; ii) contacting isolated nucleic acid with oligonucleotide primers specific for amplifying, in the SMAD4 gene: A at position 1498, G at position 1498, T at position 1499, C at position 1499, A at position 1500 and G at position 1500, and if amplification products generated in said step of contacting indicate that A is present at position 1498, T is present at position 1499 and A is present at position 1500 of the SMAD4 gene, then concluding that the subject does not have and is not at risk of having Myhre Syndrome; and if G is present at position 1498, or if C is present at position 1499 or if G is present at position 1500 of the SMAD4 gene, then concluding that said subject has or is at risk of having Myhre Syndrome.

12 . A method for diagnosing or predicting Myhre Syndrome, or a risk of Myhre Syndrome, in a subject, which method comprises
detecting, in a sample from the subject, a mutation in SMAD4 gene by contacting SMAD4 protein in the sample with i) antibodies that specifically recognize isoleucine (I) at position 500 in the SMAD4 protein (SEQ ID NO: 2), ii) antibodies that specifically recognize methionine (M) at position 500 in the SMAD4 protein (SEQ ID NO: 2), iii) antibodies that specifically recognize threonine (T) at position 500 in the SMAD4 protein (SEQ ID NO: 2), and iv) antibodies that specifically recognize valine (V) at position 500 in the SMAD4 protein (SEQ ID NO: 2); and, if M, T or V is detected at position 500 in the SMAD4 protein (SEQ ID NO: 2), then concluding that said subject has or is at risk of having Myhre Syndrome; and if I is detected at position 500 in the SMAD4 protein (SEQ ID NO: 2), then concluding that said subject does not have and is not at risk of having Myhre Syndrome.

13 . A method of treating Myhre Syndrome in a subject in need thereof, comprising
administering to said subject a therapeutically effective amount of an inhibitor of the SMAD4-mediated transforming growth factor β/bone morphogenic protein (TGFβ/BMP) signaling pathway.

Assignees

• Cormier-Daire Valerie
• Le Goff Carine
• Munnich Arnold
• Inserm (Institut Nat De La Sante Et De La Rech Medicale)
• Univ Paris Descartes - Paris V

Inventors

• Cormier-Daire Valerie
• Le Goff Carine
• Munnich Arnold

Classifications

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• C12N15/1136

  against growth factors, growth regulators, cytokines, lymphokines or hormones · CPC title

• G01N2800/10

  Musculoskeletal or connective tissue disorders · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• C07K16/22

  against growth factors {; against growth regulators} · CPC title