Method and drug for treating spinal muscular atrophy

Abstract

The present application relates to a method for treating spinal muscular atrophy (SMA), comprising: administering a therapeutically effective amount of a plasminogen pathway activator to a subject. The present application also relates to a pharmaceutical composition, product, and kit comprising said plasminogen pathway activator, which are used for treating spinal muscular atrophy.

1 . A method for treating spinal muscular atrophy (SMA), comprising: administering a therapeutically effective amount of a plasminogen pathway activator to a subject suffering from spinal muscular atrophy (SMA). 
     
     
         2 . The method according to  claim 1 , wherein the plasminogen pathway activator promotes transcription and/or expression of the SMN gene. 
     
     
         3 . The method according to  claim 1 , wherein the plasminogen pathway activator improves one or more of the following conditions of the subject: muscle strength, muscle tone, motor function, respiratory function, and muscle atrophy. 
     
     
         4 . The method according to  claim 1 , wherein the plasminogen pathway activator prolongs survival time of the subject. 
     
     
         5 . The method according to  claim 1 , wherein the plasminogen pathway activator promotes expression of NF-κB protein in the subject. 
     
     
         6 . The method according to  claim 1 , wherein the plasminogen pathway activator has one or more of the following effects:
 1) promoting penetration of plasminogen through the blood-brain barrier and the blood-spinal cord barrier,   2) promoting aggregation of plasminogen to the brain and spinal cord tissue of SMA subjects,   3) promoting aggregation of plasminogen to the injured tissue of SMA subjects,   4) increasing plasminogen levels in brain and spinal cord of SMA subjects,   5) increasing the level of local plasminogen in the injured tissue of SMA subjects,   6) alleviating damage to the injured tissue of SMA subjects,   7) promoting repair of inflammation of the injured tissue of SMA subjects,   8) promoting transcription of SMNΔ7 in brain and spinal cord of SMA subjects,   9) increasing SMN protein levels in brain and spinal cord of SMA subjects,   10) promoting expression of NGF in brain and spinal cord of SMA subjects, and   11) promoting growth and development of SMA subjects.   
     
     
         7 . The method according to  claim 1 , wherein the plasminogen pathway activator is administered in combination with one or more other medicaments or therapies. 
     
     
         8 . The method according to  claim 1 , wherein the plasminogen pathway activator is administered by nasal inhalation, aerosol inhalation, nasal drops, eye drops, ear drops, intravenous administration, intraperitoneal administration, subcutaneous administration, intracranial administration, intrathecal administration, intra-arterial administration (e.g., via the carotid artery) or intramuscular administration. 
     
     
         9 . The method according to  claim 1 , wherein the plasminogen pathway activator is a component of the plasminogen activation pathway. 
     
     
         10 . The method according to  claim 9 , wherein the component of the plasminogen activation pathway is plasminogen. 
     
     
         11 . The method according to  claim 10 , wherein the plasminogen is human full-length plasminogen or a conservatively substituted variant thereof. 
     
     
         12 . The method according to  claim 10 , wherein the plasminogen has at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 2, and has the lysine binding activity or proteolytic activity of plasminogen. 
     
     
         13 . The method according to  claim 10 , wherein the plasminogen is a protein comprising an amino acid sequence having at least 80%, 90%, 95%, 96%, 97%, 98% or 99% amino acid sequence identity with SEQ ID NO: 14, and has the proteolytic activity of plasminogen. 
     
     
         14 . The method according to  claim 10 , wherein the plasminogen is selected from the group consisting of Glu-plasminogen, Lys-plasminogen, mini-plasminogen, micro-plasminogen, delta-plasminogen, and variants thereof retaining the proteolytic activity of plasminogen. 
     
     
         15 . The method according to  claim 10 , wherein the plasminogen comprises an amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12, or comprises a conservatively substituted variant of the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12.