Methods of treating friedreich's ataxia using src inhibitors

Abstract

In one aspect, the invention presents a method of treating Friedreich's ataxia (FRDA) by administering a therapeutically effective amount of an Src inhibitor.

1 . A method of treating Friedreich's ataxia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a Src inhibitor or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1 , wherein the subject is a human. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the Src inhibitor inhibits Y118 phosphorylation of frataxin. 
     
     
         5 . The method of  claim 1 , wherein the Src inhibitor is a SrcY527F antagonist. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the Src inhibitor increases endogenous frataxin levels by at least 25% over an inactive control. 
     
     
         8 . The method of  claim 1 , wherein the Src inhibitor increases endogenous frataxin levels by at least 50% over an inactive control. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the Src inhibitor increases endogenous frataxin levels by at least 100% over an inactive control. 
     
     
         11 . The method of  claim 1 , wherein the Src inhibitor is selected from the group consisting of saracatinib (AZD-530), dasatinib, bafetinib, KX01, XL228, DCC-2036, ponatinib (AP24534), and TG100435. 
     
     
         12 . The method of  claim 1 , wherein the Src inhibitor is selected from the group consisting of SU6656, PP2, dasatinib, bafetinib, saracatinib, XL999, KX01, XL228, and bosutinib. 
     
     
         13 . The method of  claim 12 , wherein the Src inhibitor is selected from the group consisting of SU6656, PP2, dasatinib, and bosutinib. 
     
     
         14 . The method of  claim 12 , wherein the Src inhibitor is dasatinib. 
     
     
         15 . The method of  claim 12 , wherein the Src inhibitor is bosutinib. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (Canceled) 
     
     
         27 . (Canceled) 
     
     
         28 . The method of  claim 1 , wherein the Src inhibitor is administered by controlled release. 
     
     
         29 . The method of  claim 1 , wherein the Src inhibitor is administered topically. 
     
     
         30 . The method of  claim 1 , wherein the Src inhibitor is administered intraveneously. 
     
     
         31 . The method of  claim 1 , wherein the Src inhibitor is administered orally. 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . A method of inhibiting ubiquitination of frataxin in a subject comprising administering to a subject a therapeutically effective amount of a Src inhibitor or a pharmaceutically acceptable salt thereof. 
     
     
         40 . The method of  claim 1 , further comprising administering to the subject one or more agents selected from the group consisting of a ubiquitination inhibitor, an antioxidant, and a siderophore. 
     
     
         41 . The method of  claim 1 , further comprising administering to the subject one or more agents selected from the group consisting of an interferon and a ubiquitin-competing molecule. 
     
     
         42 . The method of  claim 41 , wherein the agent is an interferon. 
     
     
         43 . The method of  claim 42 , wherein the interferon is gamma interferon. 
     
     
         44 . (canceled)