Lingo-2 antagonists for treatment of conditions involving motor neurons

Abstract

The invention provides methods of treating diseases, disorders or injuries involving motor neuron survival and axonal growth, including amylotrophic lateral sclerosis, by the administration of a LINGO-2 antagonist.

1 .- 56 . (canceled) 
     
     
         57 . An antibody or antigen-binding fragment thereof that preferentially binds to LINGO-2, wherein the antibody or antigen-binding fragment thereof is capable of: (i) promoting survival of a motor neuron; and/or (ii) decreasing inhibition of axonal growth of a motor neuron. 
     
     
         58 . The antibody or antigen-binding fragment thereof of  claim 57 , wherein the LINGO-2 antibody or antigen-binding fragment does not bind LINGO-1. 
     
     
         59 . A method for promoting survival of a motor neuron or promoting axonal growth of a motor neuron, the method comprising contacting the motor neuron with an effective amount of a LINGO-2 antagonist selected from the group consisting of:
 (i) a soluble LINGO-2 polypeptide;   (ii) a LINGO-2 antibody or antigen-binding fragment thereof that preferentially binds LINGO-2;   (iii) a LINGO-2 antagonist polynucleotide;   (iv) a LINGO-2 aptamer; and   (v) a combination of two or more of the LINGO-2 antagonists.   
     
     
         60 . The method of  claim 59 , comprising (a) transfecting the motor neuron with a polynucleotide which encodes the LINGO-2 antagonist through operable linkage to an expression control sequence, and (b) allowing expression of the LINGO-2 antagonist. 
     
     
         61 . A method for treating a disease, disorder, or injury associated with survival of a motor neuron or with axonal growth of motor neurons in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of a composition comprising a LINGO-2 antagonist selected from the group consisting of:
 (i) a soluble LINGO-2 polypeptide;   (ii) a LINGO-2 antibody or antigen-binding fragment thereof that preferentially binds LINGO-2;   (iii) a LINGO-2 antagonist polynucleotide;   (iv) a LINGO-2 aptamer; and   (v) a combination of two or more of the LINGO-2 antagonists.   
     
     
         62 . The method of  claim 61 , wherein the LINGO-2 antagonist is a soluble LINGO-2 polypeptide. 
     
     
         63 . The method of  claim 61 , wherein the LINGO-2 antagonist is a LINGO-2 antibody or antigen-binding fragment thereof that preferentially binds LINGO-2. 
     
     
         64 . The method of  claim 61 , wherein the human subject has been diagnosed with a disease, disorder, or injury involving motor neurons. 
     
     
         65 . The method of  claim 61 , wherein the disease, disorder, or injury is selected from the group consisting of amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), hereditary spastic paraparesis (HSP), X-linked spinobulbar muscular atrophy (SBMA; Kennedy disease), progressive bulbar palsy, pseudo-bulbar palsy, spinal muscular atrophy (SMA), post-polio syndrome (PPS), Huntington's disease, Essential tremor (ET), motor neuron disease, paralysis, and Parkinson's disease. 
     
     
         66 . The method of  claim 61 , wherein the disease, disorder, or injury is amyotrophic lateral sclerosis (ALS). 
     
     
         67 . The method of  claim 63 , wherein the LINGO-2 antibody or antigen-binding fragment does not bind LINGO-1. 
     
     
         68 . The method of  claim 61 , wherein the LINGO-2 antagonist is administered by bolus injection or chronic infusion. 
     
     
         69 . The method of  claim 61 , wherein the LINGO-2 antagonist is administered directly into the central nervous system. 
     
     
         70 . The method of  claim 61 , wherein the LINGO-2 antagonist is administered systemically. 
     
     
         71 . An isolated nucleic acid comprising a polynucleotide encoding a soluble fragment of the polypeptide of SEQ ID NO:2, or a variant thereof, wherein the polypeptide is capable of promoting survival of a motor neuron. 
     
     
         72 . A vector comprising the nucleic acid of  claim 71 . 
     
     
         73 . A host cell comprising the nucleic acid of  claim 71  or the vector of  claim 72 .