Cerebrospinal fluid purification system
The present invention provides methods and systems for conditioning cerebrospinal fluid (CSF) by removing target compounds from CSF. The systems provide for a catheter flow path and exchange of a majority volume portion of CSF in the CSF space. The removal and/or delivery of specific compounds can be tailored to the pathology of the specific disease. The removal is targeted and specific, for example, through the use of specific size-exclusion thresholds, antibodies against specific toxins, and other chromatographic techniques, as well as delivery and/or removal of targeted therapeutic agents.
1 . A system for conditioning cerebrospinal fluid (CSF), said system comprising:
a catheter assembly including a first lumen with a plurality of inflow openings and a second lumen with a plurality of outflow openings, said catheter assembly being adapted to be introduced in a CSF space, each of the plurality of inflow openings being spaced an adjustable distance axially apart from each of the plurality of outflow openings;
a pump connectable between the first and second lumens to induce a flow of CSF therebetween; and
a conditioning component connectable between the first and second lumens to condition the CSF flowing therebetween,
and wherein the catheter assembly is configured as a closed loop system to withdraw CSF through the plurality of inflow openings and return CSF through the plurality of outflow openings at substantially the same rate without any artificial cerebrospinal fluid.
2 . The system of claim 1 , wherein the pump has a flow rate adjustable between 0.04 ml/min to 30 ml/min.
3 . The system of claim 1 , wherein the pump comprises a peristaltic pump which is isolated from the CSF flow.
4 . The system of claim 1 , wherein the condition component is selected from the group consisting of size exclusion, immunoaffinity, biospecific affinity, cationic exchange, anionic exchange and hydrophobicity.
5 . The system of claim 1 , wherein the system has a CSF retention volume below 40 ml.
6 . The system of claim 1 , wherein the conditioning component is configured to remove at least one of erythrocytes, hemoglobin, oxyhemoglobin and endothelin from the CSF.
7 . The system of claim 1 , wherein the conditioning component is configured to remove at least one of alpha-synuclein fibrils and oligomers from the CSF.
8 . The system of claim 1 , wherein the conditioning component is configured to remove at least one of insoluble superoxide dismutase-1 (SOD1), glutamate, neurofilament protein, and anti-GM1 ganglioside antibodies from the CSF.
9 . The system of claim 1 , wherein the conditioning component is configured to remove at least one of tumor necrosis factor-alpha (TNFa) and IgG from the CSF.
10 . The system of claim 1 , wherein the conditioning component is configured to remove at least one of cells and inflammatory mediators selected from the group consisting of C5a, TNF a, IL-2, IL-6, interferon-y, IgG, and endotoxins from the CSF.
11 . The system of claim 1 , wherein the conditioning component is configured to remove at least one of T cells, B cells, anti-myelin antibodies and inflammatory mediators selected from the group consisting of TNF-a, IL-2, IL-6, interferon-y from the CSF.
12 . The system of claim 1 , wherein the conditioning component is configured to remove at least one of endothelin and enolase from the CSF.
13 . A system for conditioning cerebrospinal fluid (CSF), the system comprising:
a catheter having a first lumen with a plurality of aspiration openings and a second lumen having a plurality of infusion openings; and wherein each of the plurality of aspiration openings are spaced an adjustable distance axially apart from each of the plurality of infusion openings; wherein the first lumen is configured to remove a cerebrospinal fluid from a first cerebrospinal fluid space in a patient through the plurality of aspiration openings; a filter coupled to the catheter, the filter being designed to remove one or more materials from the cerebrospinal fluid and to form a conditioned cerebrospinal fluid; wherein the second lumen is configured to return the conditioned cerebrospinal fluid to a second cerebrospinal fluid space through the plurality of infusion openings; and wherein the system is configured as a closed loop system such that cerebrospinal fluid is removed from the patient at a first flow rate, wherein the conditioned cerebrospinal fluid is returned to the patient at a second flow rate that is substantially the same as the first flow rate without any artificial cerebrospinal fluid.
14 . The system of claim 13 , wherein the system is configured such that the flow directions of removing the cerebrospinal fluid and returning the conditioned cerebrospinal fluid are periodically reversed.
15 . The system of claim 13 , wherein the filter is designed to remove meningitis-related substances.
16 . The system of claim 13 , wherein the filter is designed to remove at least one of blood cells, hemoglobin, oxyhemoglobin, endothelin or inflammatory mediators from the CSF.
17 . The system of claim 13 , wherein the filter is designed to remove at least one of AO or tau proteins or inflammatory mediators from the CSF.
18 . The system of claim 13 , wherein the filter is designed to remove at least one of cells and inflammatory mediators selected from the group consisting of C5a, TNP-a, IL-2, IL-6, interferon-v, IgG, and endotoxins from the CSF.
19 . The system of claim 13 , further including one or more sensors for intermittent or continuous monitoring or sampling the cerebrospinal fluid for levels of one or more specific compounds or parameters of interest, wherein one or more sensors are utilized to serially sample and quantify levels of a specific compound or molecule in the CSF, and be used as an indication of how much the system has conditioned the CSF.
20 . A method for conditioning cerebrospinal fluid (CSF), the method comprising:
removing cerebrospinal fluid from a first location in a cerebrospinal fluid space of the patient with a catheter assembly, the catheter assembly comprising:
a first lumen with a plurality of inflow openings and a second lumen with a plurality of outflow openings, said catheter assembly being adapted to be introduced in a CSF space, each of the plurality of inflow openings being spaced an adjustable distance axially apart from each of the plurality of outflow openings;
a pump connectable between the first and second lumens to induce a flow of CSF therebetween; and
a conditioning component connectable between the first and second lumens to condition the CSF flowing therebetween;
conditioning the cerebrospinal fluid with the conditioning component; and
returning the conditioned cerebrospinal fluid to the patient at a second location in the cerebrospinal fluid space of the patient, wherein the cerebrospinal fluid is returned to the patient at substantially the same flow rate at which it is removed;
wherein the conditioned cerebrospinal fluid is free of artificial cerebrospinal fluid.