Methods for distributing agents to areas of brain
Broad cerebrospinal fluid (CSF) distribution of an agent is achievable by delivering the agent in a liquid formulation to the CSF at flow rates less than 500 microliters per hour, such as between about 2 microliters per hour and about 100 microliters per hour.
1. A method comprising:
selecting a subject for which delivery of a therapeutic or diagnostic molecule to cerebrospinal fluid (CSF) of a brain is desired; and
administering a liquid formulation comprising the molecule to an CSF-containing intrathecal space of the subject at a flow rate of less than 500 microliters per hour, wherein the liquid formulation is administered for a period of time sufficient to reach a steady state concentration in CSF of the brain, and wherein the molecular weight of the molecule is less than 5 kDa, between 15 kDa and 200 kDa, greater than 200 kDa, or a polypeptide or antisense DNA having a molecular weight of between 5 kDa and 15 kDa, and wherein the molecule is generally distributed throughout at least most of the CSF of the brain at therapeutically or diagnostically effective concentrations.
2. A method according to claim 1 , wherein the liquid formulation is administered at a flow rate of less than 200 microliters per hour.
3. A method according to claim 1 , wherein the liquid formulation is administered at a flow rate of between about 4 microliters per hour and about 100 microliters per hour.
4. A method according to claim 1 , wherein the liquid formulation is administered at a flow rate of between about 2 microliters per hour and about 25 microliters per hour.
5. A method according to claim 1 , wherein the liquid formulation is delivered via a catheter having a delivery region placed in the CSF-containing space.
6. A method according to claim 5 , wherein the CSF-containing space is selected from the group consisting of lumbar intrathecal space, thoracic intrathecal space, and cervical intrathecal space.
7. A method according to claim 1 , further comprising administering the liquid formulation at a second slower rate for a period of time sufficient to reduce the concentration of the molecule in the CSF.
8. A method according to claim 7 , wherein the liquid formulation is administered via a catheter, and wherein the second slower rate is sufficient to keep the catheter patent.
9. A method comprising:
selecting a subject for which broad distribution of a therapeutic or diagnostic molecule in cerebrospinal fluid (CSF) of the subject is desired; and
administering a liquid formulation comprising the molecule to the CSF at a flow rate of less than 500 microliters per hour, wherein the liquid formulation is administered for a period of time sufficient to reach a steady state concentration in the CSF, and wherein the molecular weight of the molecule is less than 5 kDa, between 15 kDa and 200 kDa, greater than 200 kDa, or a polypeptide or antisense DNA having a molecular weight of between 5 kDa and 15 kDa and wherein the molecule is generally distributed throughout at least most of the CSF of the brain at therapeutically or diagnostically effective concentrations.
10. A method according to claim 9 , wherein the liquid formulation is administered at a flow rate of less than 200 microliters per hour.
11. A method according to claim 9 , wherein the liquid formulation is administered at a flow rate of between about 4 microliters per hour and about 100 microliters per hour.
12. A method according to claim 9 , wherein the liquid formulation is administered at a flow rate of between about 2 microliters per hour and about 25 microliters per hour.
13. A method according to claim 9 , wherein the liquid formulation is delivered via a catheter having a delivery region placed in the CSF.
14. A method according to claim 13 , wherein the delivery region is positioned in a CSF location selected from the group consisting of lumbar intrathecal space, thoracic intrathecal space, cervical intrathecal space, cisterna magna, subdural space, subarachnoid space, and the intracerebroventricular space.
15. A method according to claim 9 , further comprising administering the liquid formulation at a second slower rate for a period of time sufficient to reduce the concentration of the molecule in the CSF.
16. A method according to claim 15 , wherein the liquid formulation is administered via a catheter, and wherein the second slower rate is sufficient to keep the catheter patent.
17. A method according to claim 14 , wherein the delivery region is positioned in the intracerebroventricular space.
18. A method according to claim 9 , wherein administering the liquid formulation comprising the molecule to the CSF comprises administering the liquid formulation to a lumbar intrathecal space.
19. A method according to claim 1 , wherein administering the liquid formulation comprising the molecule to the CSF-containing intrathecal space comprises administering the liquid formulation to a lumbar intrathecal space.