Neuregulin for the treatment and/or prevention of tumors of the nervous system

Abstract

A polypeptide is provided that includes an EGF-like domain of a neuregulin protein. A nucleic acid encoding for the polypeptide is also provided. A gene therapy vector inclusive of the nucleic acid and genetically modified cells expressing said polypeptide are also provided. The medical use of the polypeptide, the nucleic acid, the gene therapy vector or the cell for the treatment of tumours of the nervous system are also provided. In particular the treatment of tumours of the cranial or peripheral nerves, tumours associated with neurofibromatosis, schwannomas, neurofibromas and malignant nerve sheath tumours are provided.

1 . A method for treating and/or preventing a tumor of the nervous system in a subject, comprising administering a nucleic acid molecule to the subject, wherein the nucleic acid molecule encodes a polypeptide that comprises an EGF-like domain of a neuregulin protein. 
     
     
         2 . The method according to  claim 1 , wherein the polypeptide is a soluble fragment of a neuregulin protein. 
     
     
         3 . The method according to  claim 1 , wherein the polypeptide comprises an amino acid sequence according to one of SEQ ID NO 9-14 or an amino acid sequence with an identity of at least 80% to any one of SEQ ID NO 9-14. 
     
     
         4 . The method according to  claim 1 , wherein the polypeptide consists of an amino acid sequence according to SEQ ID NO 9 or of an amino acid sequence with an identity of at least 80% to SEQ ID NO 9. 
     
     
         5 . The method according to  claim 1 , wherein the tumor is a tumor of the cranial or peripheral nerves. 
     
     
         6 . The method according to  claim 1 , wherein the tumor is a malignant nerve sheath tumor. 
     
     
         7 . The method according to  claim 1 , wherein the tumor is a schwannoma. 
     
     
         8 . The method according to  claim 1 , wherein the tumor is a neurofibroma. 
     
     
         9 . The method according to  claim 1 , for treating and/or preventing medical conditions associated with one or more of genetic deficiency in neurofibromatosis type 1, neurofibromatosis type 2, or neurofibromatosis type 3. 
     
     
         10 . The method according to  claim 1 , wherein the nucleic acid molecule comprises a gene therapy vector. 
     
     
         11 . The method according to  claim 10 , wherein the gene therapy vector is a viral vector. 
     
     
         12 . The method according to  claim 11 , wherein viral vector is selected from the group consisting of a moloney murine leukemia virus (MMLV), an adenoviral vector, a lentiviral vector, an adenovirus-associated viral (AAV) vector, a pox virus vector, a herpes simplex virus vector or human immunodeficiency virus vector (HIV-1). 
     
     
         13 . The method according to  claim 10 , wherein the gene therapy vector is a non-viral vector. 
     
     
         14 . The method according to  claim 13 , wherein the gene therapy vector is transferred by electroporation or injection of nucleic acid molecule into the subject. 
     
     
         15 . The method according to  claim 13 , wherein the gene therapy vector is a plasmid DNA expression vector driven by a eukaryotic promoter, or liposomes encapsulating the vector. 
     
     
         16 . The method according to  claim 10 , wherein the gene therapy vector is configured for inducible or conditional expression of the polypeptide. 
     
     
         17 . The method according to  claim 1 , comprising administering a cell to the subject, wherein the cell is genetically modified to comprise the nucleic acid molecule according to  claim 1 . 
     
     
         18 . The method according to  claim 1 , wherein the nucleic acid molecule is configured to incorporate into the genome of a host cell of the subject. 
     
     
         19 . The method according to  claim 1 , wherein the composition is administered intravenously to the subject. 
     
     
         20 . The method according to  claim 1 , wherein the composition is administered locally to the site of the tumor.