Methods and compositions for modulation of blood-neural barrier
Methods and compositions for modulating blood-neural barrier (BNB) for the treatment of CNS conditions such as edema, and for increased drug delivery efficacy across the BNB. The present invention further relates to improved tPA treatment of ischemic cerebrovascular and related diseases in combination with antagonism of the PDGF signaling pathway. The inventive method and composition is particularly suitable for conjunctive therapy of ischemic stroke using tPA and an anti-PDGF-C antagonist or an anti-PDGFR-α antagonist.
1. A method for treating neural edema in a higher vertebrate animal in need of such treatment comprising administering to said animal an effective amount of an anti-PDGF-CC antibody or an anti-PDGF-C antibody.
2. The method of claim 1 wherein the animal is a mammal.
3. The method of claim 1 wherein the animal is a human.
4. The method of claim 1 wherein the antibody is a monoclonal antibody.
5. The method of claim 1 wherein the antibody is a chimeric, humanized or fully-human antibody.
6. The method of claim 1 wherein the antibody is administered intravenously.
7. The method of claim 1 wherein the antibody is delivered by injection.
8. The method of claim 1 wherein the neural edema is associated with administration of tissue-type plasminogen activator (tPA).
9. The method of claim 8 wherein the anti-PDGF-CC antibody binds specifically to the tPA proteolytic site of PDGF-CC.
10. A method for treating stroke in a higher vertebrate animal suffering from stroke comprising administering to said animal an effective amount of an anti-PDGF-CC antibody or an anti-PDGF-C antibody in combination with tissue-type plasminogen activator (tPA).
11. The method of claim 10 wherein the animal is a mammal.
12. The method of claim 10 wherein the animal is a human.
13. The method of claim 10 wherein the antibody is a monoclonal antibody.
14. The method of claim 10 wherein the antibody is a chimeric, humanized or fully-human antibody.
15. The method of claim 10 wherein the antibody is administered intravenously.
16. The method of claim 10 wherein the antibody is delivered by injection.
17. The method of claim 10 wherein the antibody and tPA are administered concurrently.
18. The method of claim 10 wherein the antibody and tPA are administered sequentially.
19. The method of claim 18 wherein the antibody is administered before tPA is administered.
20. The method of claim 18 wherein the antibody is administered after tPA is administered.
21. The method of claim 10 wherein the stroke is ischemic stroke.