Transdiscal Administration of Specific Inhibitors of Pro-Inflammatory Cytokines
The present invention relates to injecting a high specificity cytokine antagonist into a diseased intervertebral disc.
1 . A method of inhibiting degeneration of an extracellular matrix of a nucleus pulposus of an intervertebral disc having a degenerating nucleus pulposus and an annulus fibrosus in a patient in need thereof, comprising transdiscally administering into the degenerating nucleus pulposus an effective amount of a formulation comprising:
a) a high specificity cytokine antagonist that inhibits tumor necrosis factor-alpha (TNF-α), and
b) one or more additional therapeutic agents selected from the group consisting of a growth factor and viable mesenchymal stem cells.
2 . The method of claim 1 , wherein the formulation comprises viable mesenchymal stem cells.
3 . The method of claim 2 , wherein the mesenchymal stem cells are autologous.
4 . The method of claim 1 , wherein the mesenchymal stem cells are provided in a concentrated form.
5 . The method of claim 1 , wherein the mesenchymal stem cells are uncultured.
6 . The method of claim 1 , wherein the formulation comprises a growth factor.
7 . The method of claim 6 , wherein the growth factor is transforming growth factor beta (TGF-β) or a bone morphogenetic protein (BMP).
8 . The method of claim 1 , wherein the high specificity cytokine antagonist is a monoclonal antibody.
9 . The method of claim 8 , wherein the monoclonal antibody is infliximab.
10 . The method of claim 1 , wherein the high specificity cytokine antagonist is etanercept.
11 . The method of claim 1 , wherein the high specificity cytokine antagonist is present in the formulation in a concentration of at least 100 mg/ml.
12 . The method of claim 1 , wherein the high specificity cytokine antagonist is present in the formulation in a dose of no more than 0.5 mg.
13 . The method of claim 1 , wherein the formulation is suitable for administration into an intervertebral disc at a volume of between 0.5 ml and about 3.0 ml.
14 . The method of claim 9 , wherein the infliximab is present at a concentration of between about 30 mg/ml and about 60 mg/ml.
15 . The method of claim 1 , wherein the formulation is delivered in a sustained release device.
16 . The method of claim 1 , wherein the high specificity cytokine antagonist inhibits the production of TNF-α, binds a membrane-bound TNF-α, binds a solubilized TNF-α or binds a receptor of TNF-α.
17 . The method of claim 3 , wherein the autologous mesenchymal stem cells are uncultured mesenchymal stem cells from about 7-10 ml of the patient's bone marrow.
18 . A method of treating degenerative disc disease in an intervertebral disc having a nucleus pulposus and annulus fibrosus in a patient, comprising transdiscally administering into the degenerating nucleus pulposus an effective amount of a formulation comprising:
a) a high specificity cytokine antagonist that inhibits tumor necrosis factor-alpha (TNF-α), and
b) one or more additional therapeutic agents selected from the group consisting of a growth factor and viable mesenchymal stem cells.
19 . The method of claim 18 , wherein the formulation is administered into the nucleus pulposus of the intervertebral disc.
20 . The method of claim 18 , wherein the formulation is administered into the annulus fibrosus of the intervertebral disc.