Cerebrospinal fluid purification system
Inventors
Lad, Shivanand • Mobley, William C. • Nikolich, Karoly • Saul, Thomas
Assignees
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Publication Number
US-9895518-B2
Publication Date
2018-02-20
Expiration Date
Abstract
The present invention provides methods and systems for conditioning cerebrospinal fluid (CSF) by removing target compounds from CSF. The systems provide for a multilumen 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.
Core Innovation
The invention provides a method for conditioning cerebrospinal fluid (CSF) in a patient having a symptom of Alzheimer's disease by introducing a catheter apparatus into a first location in a CSF space and withdrawing endogenous CSF through a distal or proximal port at a first flow rate. The withdrawn CSF is conditioned and then returned to the patient at a second location in the CSF space through the other of the ports at a second flow rate. The withdrawing and returning steps are performed concurrently during at least a portion of a conditioning treatment, and the first and second flow rates are substantially the same rate.
The method further includes a primed-system infusion such that, while an initial volume of endogenous CSF is withdrawn from the first location through one port, a volume of fluid from a primed system is infused at substantially the same rate through the other port. Conditioning includes conditioning the withdrawn CSF by withdrawing proteins selected from a group consisting of tau proteins, IL-1, IL-2, IL-6, IL-12, and interferon-gamma.
Protein withdrawal is carried out using a combination of size, biospecific affinity, and charge-based selection criteria by contacting CSF with multiple substrates. In addition, conditioning comprises processing CSF over an antibody cartridge comprising antibodies or antibody fragments secured to an ex-vivo immunoaffinity column, with periodically re-using or re-charging the antibody cartridge using an eluent to release captured proteins and regenerate active antigen binding sites of the antibodies or antibody fragments.
Claims Coverage
The independent claims cover a CSF conditioning method for an Alzheimer's disease patient that uses a dual-port catheter apparatus to concurrently withdraw and return CSF at substantially the same flow rate, combined with protein conditioning based on size, biospecific affinity, and charge selection, including immunoaffinity cartridge processing with optional periodic re-use/regeneration.
Concurrent dual-port CSF conditioning at substantially the same flow rate
A method for conditioning CSF by introducing a catheter apparatus with a distal port and a proximal port spaced axially apart, withdrawing endogenous CSF from a first CSF-space location through one port at a first flow rate, conditioning the withdrawn CSF, and returning the conditioned CSF to a second CSF-space location through the other port at a second flow rate, wherein the withdrawing and returning steps are performed concurrently during at least a portion of a conditioning treatment and the first and second flow rates are substantially the same rate.
Primed-system infusion during initial withdrawal
The method further wherein, while an initial volume of endogenous CSF is withdrawn from the first location through one port, a volume of fluid from a primed system is infused at substantially the same rate through the other port.
Protein conditioning by multi-criteria selection from conditioned CSF
Conditioning the withdrawn CSF comprises withdrawing proteins selected from a group consisting of tau proteins, IL-1, IL-2, IL-6, IL-12, and interferon-gamma, wherein withdrawing proteins selected from the group comprises withdrawing proteins using a combination of size, biospecific affinity, and charge-based selection criteria by contacting CSF with multiple substrates.
Antibody cartridge immunoaffinity processing with eluent regeneration
Conditioning comprises processing CSF over an antibody cartridge comprising antibodies or antibody fragments secured to an ex-vivo immunoaffinity column, and wherein the method further comprises periodically re-using or re-charging the antibody cartridge, including using an eluent to release captured proteins and regenerate active antigen binding sites of the antibodies or antibody fragments.
Across the independent claims, the core coverage is for concurrent CSF withdrawal and return using a spaced distal/proximal catheter apparatus at substantially the same flow rate, with primed-system infusion during initial withdrawal, and protein conditioning that withdraws specified Alzheimer's-related protein targets using combined size, biospecific affinity, and charge-based multi-substrate selection, including optional ex-vivo antibody cartridge immunoaffinity processing with eluent-based regeneration.
Stated Advantages
Documented Applications
Conditioning CSF for a patient having a symptom of Alzheimer's disease by withdrawing and returning conditioned CSF using the described concurrent dual-port catheter apparatus and specified protein-target conditioning.
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