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US-12616822-B2 - Cerebrospinal fluid purification system

US12616822B2US 12616822 B2US12616822 B2US 12616822B2US-12616822-B2

Abstract

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.

Inventors

  • Shivanand Lad
  • William C. Mobley
  • Karoly Nikolich
  • Thomas Saul

Assignees

  • PHARAOH NUERO, INC.

Dates

Publication Date
20260505
Application Date
20210622

Claims (20)

  1. 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. 2 . The system of claim 1 , wherein the pump has a flow rate adjustable between 0.04 ml/min to 30 ml/min.
  3. 3 . The system of claim 1 , wherein the pump comprises a peristaltic pump which is isolated from the CSF flow.
  4. 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. 5 . The system of claim 1 , wherein the system has a CSF retention volume below 40 ml.
  6. 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. 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. 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. 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. 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. 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. 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. 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. 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. 15 . The system of claim 13 , wherein the filter is designed to remove meningitis-related substances.
  16. 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. 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. 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. 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. 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.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS The present application is a continuation of U.S. patent application Ser. No. 16/548,554, filed Aug. 22, 2019; which is a continuation of U.S. patent application Ser. No. 15/410,219, filed Jan. 19, 2017, now U.S. Pat. No. 10,398,884; which is a continuation of U.S. patent application Ser. No. 13/801,215, filed Mar. 13, 2013, now U.S. Pat. No. 9,895,518; which is a continuation of U.S. patent application Ser. No. 12/444,581, filed Jul. 1, 2010, now U.S. Pat. No. 8,435,204; which is the U.S. National Phase entry of International Patent Application No. PCT/US2007/080834, filed Oct. 9, 2007, which claims the benefit of U.S. Provisional Application No. 60/828,745, filed Oct. 9, 2006. The entireties of the above-captioned applications are incorporated by reference herein for all purposes. FIELD OF THE INVENTION The invention pertains generally to medical devices and methods. More particularly, the present invention relates to devices, systems methods and kits for removal of toxins from the cerebrospinal fluid (CSF). More specifically, the method and system can be used to diagnose and treat disorders affecting the central nervous system (CNS) by measuring and modifying the chemical composition of CSF. BACKGROUND OF THE INVENTION Others have described devices for the handling and/or removal of cerebrospinal fluid (CSF) to and from a patient. For example, several patents disclose various methods for diverting or shunting CSF from the CSF space (ventricle, spinal column) to another portion of the body (e.g., abdomen, peritoneal cavity). See, e.g., U.S. Pat. Nos. 2,969,066; 3,889,687; 6,575,928 and 7,118,549. Others have described administering therapeutic agents to the CSF space, but do not disclose removing the CSF. See, e.g., U.S. Pat. Nos. 5,531,673; 6,056,725; 6,594,880; 6,682,508 and 6,689,756. Generally, the therapeutic agents are locally delivered to the brain but not to the greater cerebrospinal fluid space, which includes the brain and the spine. Others disclose removing CSF, but generally do not administer therapeutic agent or any other fluid. See, e.g.; U.S. Pat. Nos. 3,889,687; 5,683,357; 5,405,316 and 7,252,659. Devices exist having both input and output catheters for administering therapeutic agents or synthetic CSF and removing endogenous CSF, but the close spatial placement of the inflow and outflow catheters do not allow for flow of CSF throughout the cerebrospinal fluid space or full CSF exchange that provides access to the complete intracranial and intraspinal CSF volume. See, e.g., U.S. Pat. Nos. 4,378,797; 4,904,237; 6,537,241 and 6,709,426. Furthermore, publications disclosing the exchange of CSF describe replacing endogenous CSF with synthetic CSF replacement fluid. See, e.g., U.S. Patent Publication No. 2003/0065309; and PCT Publication Nos. WO 01/154766 and WO 03/015710. In this way, the concentration of the toxic species may be diluted but not removed. It has been proposed to treat drug overdose or removal of tumor cells to clear debris before implantation of a ventriculo-peritoneal shunt shunt system. Such an apparatus is unnatural in that it requires flushing the entire system with an artificially produced solution rather than removing the toxins of interest from the patient's endogenous CSF, requires liters of instilled replacement fluid to be delivered on a regular basis, is neither targeted nor focused for removal of specific toxins of interest and is only practical in an acute setting where liters of fluid could be instilled. See, e.g. PCT Publication No. WO 01/54766. Various devices aimed at accessing the CSF or indirectly targeting the nervous system exist, however there exists no CSF purification system that allows for the direct, targeted, logical and disease-specific removal of one or more of target compounds or the use of a dual or multi-lumen catheter that influences or controls CSF flow, mixing and efficiency of turnover. It is desirable to provide a method and system for processing and removal of one or more target compounds from the CSF of a patient. Recently, a treatment for Alzheimer's disease was suggested which relied on removal of CSF by diversion of the fluid from the brain (ventricular system) to another portion of the patients body (e.g. abdomen/peritoneal cavity) using a modified ventriculo-peritoneal shunt system. See, e.g., U.S. Pat. Nos. 5,980,480 and 7,025,742. By continuously draining CSF at a low rate, the rationale was that the body's daily production of new CSF would dilute the concentration of contaminating substances remaining in the endogenous CSF. Such a system has several inherent limitations. The rate at which the concentration of toxic species is lowered is mediated by passive flow, is very slow, addresses only a fraction (milliliters) of the total CSF volume per hour, is not targeted or focused in removing specific items of interest and does not prevent reabsorption of toxic species back into the systemic circu