Laminins, derivatives, and compositions including same and methods for their therapeutic use

Abstract

In various embodiments, the present disclosure provides a method of treating a subject using laminin or a composition that includes laminin. In one embodiment, the method is used to enhance muscle regeneration, maintenance, or repair in a subject. In another embodiment, the method is used to promote wound healing. The method, in yet another embodiment, is used to prevent or reduce muscle damage or injury. In specific implementations of these methods, the laminin or composition that includes laminin is administered in a therapeutically effective amount. In some implementations, the laminin is a complete laminin protein. In other implementations, the laminin is a laminin fragment, a laminin derivative, or a laminin analogue.

1 . A method of enhancing muscle regeneration or repair in a subject comprising systemically administering a therapeutically effective amount of a composition comprising laminin-1 and a chelating agent to the subject in need thereof. 
     
     
         2 . The method of  claim 1 , wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA). 
     
     
         3 . The method of  claim 1 , wherein subject has Duchenne muscular dystrophy. 
     
     
         4 . The method of  claim 1 , where the subject has a congential muscular dystrophy. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , further comprising diagnosing the subject with a condition characterized by impaired muscle regeneration prior to administering a therapeutically effective amount of a composition comprising laminin-1 and a chelating agent to the subject. 
     
     
         8 . The method of  claim 1 , wherein the subject has a condition characterized by impaired production of a component of the costamere, of dystrophin, laminin, or α7β1 integrin. 
     
     
         9 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , further comprising administering with the composition an additional therapeutic agent selected from a costamere protein, satellite cells, stem cells, and myocytes. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the composition is administered systemically prior to the subject experiencing muscle damage or disease. 
     
     
         15 .- 17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the composition comprises laminin-1 in an amount between about 0.01 μg/kg and about 1000 mg/kg of the subject's weight, such as 0.1 mg/kg and about 1000 mg/kg of the subject's weight or about 0.2 mg/kg and about 2 mg/kg of the subject's weight. 
     
     
         19 . A method of promoting wound healing in a subject comprising systemically administering an effective amount of a composition comprising laminin-1 and a chelating agent to the subject. 
     
     
         20 . A method of enhancing muscle regeneration or repair in a subject comprising systemically administering an effective amount of a composition comprising at least a portion of the α1 chain of laminin-1 and a chelating agent to the subject in need thereof. 
     
     
         21 . The method of  claim 20 , wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA). 
     
     
         22 . The method of  claim 20 , wherein the subject has a congenital muscular dystrophy. 
     
     
         23 . The method of  claim 22 , wherein the congenital muscular dystrophy comprises merosin deficient congenital muscular dystrophy (MCMD). 
     
     
         24 . The method of  claim 20 , wherein the subject has Duchenne muscular dystrophy. 
     
     
         25 . The method of  claim 20 , wherein systemically administering comprises systemically administering a single dose of the composition once every week to a subject in need thereof. 
     
     
         26 . The method of  claim 1 , wherein systemically administering comprises systemically administering a single dose of laminin-1 once every week to the subject in need thereof. 
     
     
         27 . The method of  claim 4 , wherein the congenital muscular dystrophy comprises merosin deficient congenital muscular dystrophy (MCMD). 
     
     
         28 . The method of  claim 1 , wherein systemically administering comprises intraperitoneal administration. 
     
     
         29 . The method of  claim 28 , wherein intraperitoneal administration comprises intraperitoneally administering a single dose of the composition intraperitoneally once every week to a subject in need thereof. 
     
     
         30 . The method of  claim 1 , wherein systemically administering comprises parenteral administration. 
     
     
         31 . The method of  claim 30 , wherein parenteral administration comprises parenterally administering a single dose of the composition parenterally once every week to a subject in need thereof. 
     
     
         32 . The method of  claim 19 , wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA). 
     
     
         33 . The method of  claim 19 , wherein the subject has a congenital muscular dystrophy. 
     
     
         34 . The method of  claim 33 , wherein the congenital muscular dystrophy comprises merosin deficient congenital muscular dystrophy (MCMD). 
     
     
         35 . The method of  claim 19 , wherein the subject has Duchenne muscular dystrophy. 
     
     
         36 . The method of  claim 19 , wherein systemically administering comprises systemically administering a single dose of the composition once every week to a subject in need thereof.