Composition and method for the treatment or prevention of spinal disorders

Abstract

The present invention provides compositions of matter suitable for the prevention of and/or treatment of a spinal disorder and/or spinal pain, e.g., caused by and/or associated with intervertebral disc (IVD) degeneration, and methods of treatment of a spinal disorder and/or spinal pain. For example, the compositions of the present invention comprise a modulator of growth differentiation factor (GDF)-6 signaling sufficient to reduce or prevent or delay IVD degeneration and/or to enhance or induce IVD regeneration. The present invention also provides medical devices comprising such compositions, and methods of treatment making use of such compositions.

1 . A method for preventing or delaying or treating a spinal disorder and/or spinal pain in a subject, said method comprising administering a modulator of GDF-6 signaling or composition comprising a modulator of GDF-6 signaling to a subject suffering from a spinal disorder and/or spinal pain for a time and under conditions sufficient to reduce, delay or prevent intervertebral disc (IVD) degeneration in the subject and/or to induce and/or enhance intervertebral disc regeneration in the subject. 
     
     
         2 .- 4 . (canceled) 
     
     
         5 . The method according to  claim 1 , wherein the modulator or composition is administered in a patterned manner. 
     
     
         6 . The method according to claim  3 , wherein the modulator or composition is administered to a plurality of sites or in a patterned manner so as to permit said modulator or composition to disperse or distribute evenly throughout the nucleus pulposus. 
     
     
         7 . The method according to  claim 1 , comprising administering the modulator or composition via a medical device comprising a delivery conduit having a proximal end attachable to a source of the modulator of GDF-6 signaling or the composition and an emitter structure at a distal end of the delivery conduit, wherein the emitter structure defines a plurality of spaced discharge apertures through which the modulator or composition is delivered. 
     
     
         8 . A method for administering a modulator of GDF-6 signaling or composition comprising a modulator of GDF-6 signaling to a subject comprising:
 accessing a region of an IVD by surgical intervention or injection;   providing or obtaining a medical device comprising the modulator or composition wherein the medical device comprises a delivery conduit having a proximal end attachable to a source of the modulator of GDF-6 signaling or the composition and an emitter structure at a distal end of the delivery conduit, wherein the emitter structure defines a plurality of spaced discharge apertures through which the modulator or composition is delivered;   inserting the emitter structure of the medical device at least partially into the accessed region of the IVD;   manipulating the emitter structure so that the emitter structure is positioned within the IVD and/or at least partially surrounds or is positioned within the nucleus pulposus and/or a region of the IVD defined by an internal wall of the annulus fibrosus; and   discharging the modulator or composition through the apertures of the device so as to administer said modulator or composition to a plurality of sites within the IVD in a single administration and/or at least partially surrounds or is positioned within the nucleus pulposus and/or a region of the IVD defined by an internal wall of the annulus fibrosus, thereby administering the modulator or composition to the subject.   
     
     
         9 . A process for preventing or delaying or treating a spinal disorder and/or spinal pain in a subject, said method comprising administering a modulator of GDF-6 signaling or composition comprising a modulator of GDF-6 signaling to a subject suffering from a spinal disorder and/or spinal pain for a time and under conditions sufficient to reduce, delay or prevent intervertebral disc (IVD) degeneration in the subject and/or to induce and/or enhance intervertebral disc regeneration in the subject, wherein said process comprises administering the modulator or composition to a subject in need thereof by performing the method of  claim 8  and resting the subject for a time and under conditions sufficient to reduce, delay or prevent intervertebral disc (IVD) degeneration and/or to induce and/or enhance intervertebral disc regeneration. 
     
     
         10 . The method according to  claim 1 , wherein the modulator of GDF-6 signaling modulates the activity and/or expression of a molecule selected from the group consisting of GDF-6, MSX-1, MSX-2, BMPR-1A, BMPR-IB, BMPR-II, Smad-1, Smad-5, Smad-8, Smad-4 and mixtures thereof. 
     
     
         11 . The method according to  claim 1 , wherein the modulator of GDF-6 signaling is a peptide or polypeptide. 
     
     
         12 . The method according to  claim 11 , wherein the peptide or polypeptide comprises GDF-6 or an active fragment thereof or an analog thereof or a derivative thereof. 
     
     
         13 .- 14 . (canceled) 
     
     
         15 . The method according to  claim 1 , comprising administering a cell comprising and/or expressing the modulator of GDF-6 signaling. 
     
     
         16 . The method according to  claim 15 , wherein the cell is a stem cell. 
     
     
         17 .- 24 . (canceled) 
     
     
         25 . A composition for modulating GDF-6 signaling in an intervertebral disc or a cell or tissue thereof sufficient to reduce, delay or prevent intervertebral disc degeneration in a subject and/or to induce and/or enhance intervertebral disc regeneration in a subject, said composition comprising
 (i) an amount of a modulator of GDF-6 signaling; and   (ii) a suitable carrier or excipient.   
     
     
         26 . The composition according to  claim 25 , wherein said composition comprises a stem cell comprising or expressing a modulator of GDF-6 signaling. 
     
     
         27 . The composition according to  claim 25 , wherein said composition comprises an amount of a modulator of GDF-6 signaling sufficient to enhance or induce collagen synthesis in an intervertebral disc or a cell or tissue thereof. 
     
     
         28 . The composition according to  claim 25 , wherein the composition is a slow release composition. 
     
     
         29 . The composition according to  claim 25 , wherein the composition has a viscosity that permits it to disperse or distribute evenly throughout the nucleus pulposus of a subject. 
     
     
         30 . A method for producing the composition of  claim 25 , said method comprising mixing or otherwise combining an amount of a modulator of GDF-6 signaling and a suitable carrier or excipient. 
     
     
         31 . The method of  claim 30 , wherein the carrier or excipient has a viscosity that permits the composition to disperse or distribute evenly throughout the nucleus pulposus of a subject. 
     
     
         32 . A medical device for modulating GDF-6 signaling in an intervertebral disc or a cell or tissue thereof sufficient to reduce, delay or prevent intervertebral disc degeneration in a subject and/or to induce and/or enhance intervertebral disc regeneration in a subject, wherein the medical device comprises:
 (i) an integer for administering an amount of a modulator of GDF-6 signaling or a composition comprising said modulator to an intervertebral disc of a subject; and   (ii) an amount of a modulator of GDF-6 signaling or an amount of the composition according to  claim 25 .   
     
     
         33 .- 35 . (canceled)