Granted Patent B2

US 12,280,229 · App. 17/354,388 · Granted Apr 22, 2025

Inventors: Shivanand Lad (Durham, NC); William C. Mobley (La Jolla, CA); Karoly Nikolich (Emerald Hill, CA); Thomas Saul (El Granada, CA)

Assignee: NEUROFLUIDICS, INC.

A61M27/006A61M25/0026A61M1/3679A61M2025/0007A61M2027/004A61M2202/0021A61M2202/0464A61M2202/203A61M2202/206A61M2206/16A61M2210/0693A61M2210/1003

Abstract

Claims (31)

1. A method for ameliorating a symptom of one or more of Amyotrophic Lateral Sclerosis and Huntington's Disease in a patient, said method comprising:

selecting a patient having a symptom of one of Amyotrophic Lateral Sclerosis or Huntington's Disease;

removing cerebrospinal fluid from a first location in a cerebrospinal fluid space of the patient;

removing a causative agent from the removed cerebrospinal fluid, thereby conditioning the cerebrospinal fluid; 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; wherein the removing and returning steps are performed concurrently using a single catheter, the single catheter comprising a first lumen with a first proximal port at the first location and a second lumen having a second distal port at the second location during at least a portion of a conditioning treatment;

wherein the first proximal port and the second distal port are axially spaced apart along the single catheter.

2. The method of claim 1 , wherein the first location is in a lumbar cerebrospinal fluid space of the patient.

3. The method of claim 1 , wherein the second location is in a cervical cerebrospinal fluid space, a thoracic cerebrospinal fluid space, or a ventricle of the patient.

4. A method as in claim 1 , wherein the method is for ameliorating a symptom of Amyotrophic Lateral Sclerosis, and wherein the step of removing includes removing at least one or more of insoluble superoxide dismutase-1 (SOD1), glutamate, neurofilament protein, and anti-GM1 ganglioside antibodies or other inflammatory mediators.

5. A method as in claim 1 , wherein the method is for ameliorating a symptom of Huntington's disease, and wherein the step of removing includes removing at least one Huntington oligomer.

6. A method as in claim 1 , wherein the flow rate is in a range from 0.04 ml/min to 30 ml/min.

7. A method as in claim 1 , wherein a volume of cerebrospinal fluid removed from the patient at any given time never exceeds 40 ml.

8. A method as in claim 1 , wherein the second location is in the cervical cerebrospinal fluid space.

9. A method as in claim 1 , wherein the second location is in the ventricle of a brain.

10. A method as in claim 1 , wherein the second location is in a thoracic cerebrospinal fluid space.

11. A method as in claim 1 , wherein flow directions of removing and returning cerebrospinal fluid are periodically reversed so that CSF is returned to the first location and removed from the second location during a portion of the treatment.

12. A method as in claim 1 , further comprising mixing the conditioned cerebrospinal fluid with endogenous cerebrospinal fluid as the conditioned cerebrospinal fluid is returned to the cerebrospinal fluid space.

13. A method as in claim 12 , wherein mixing comprises inducing a turbulent flow as the conditioned cerebrospinal fluid is returned.

14. A method as in claim 1 , wherein the conditioning comprises one or more separation processes selected from the group consisting of biospecific affinity, immunoaffinity, cationic exchange, anionic exchange, hydrophobicity, and size exclusion.

15. A method as in claim 1 , wherein the causative agent is removed from the CSF using one or more of an immunoaffinity column, a size exclusion column, an anionic exchange column, a cationic exchange column, a Protein A column, or a Protein G column.

16. A method as in claim 1 , wherein the conditioning step is performed externally to the patient's body.

17. A method for ameliorating a symptom of one or more of Amyotrophic Lateral Sclerosis and Huntington's Disease in a patient, the method comprising:

selecting a patient having a symptom of one of Amyotrophic Lateral Sclerosis or Huntington's Disease;

removing cerebrospinal fluid from a first location in a cerebrospinal fluid space of the patient;

removing a causative agent from the removed cerebrospinal fluid, thereby conditioning the cerebrospinal fluid;

wherein removing the causative agent from the removed cerebrospinal fluid includes one or more separation processes selected from the group comprising biospecific affinity, cationic exchange, anionic exchange, and hydrophobicity;

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 removing and returning steps are performed concurrently using a single catheter, the single catheter comprising a first lumen with a first proximal port at the first location and a second lumen having a second distal port at the second location during at least a portion of a conditioning treatment; and

wherein the first proximal port and the second distal port are axially spaced apart along the single catheter.

18. The method of claim 17 , wherein the conditioned cerebrospinal fluid is free of artificial cerebrospinal fluid.

Continuity (6)

References Cited (398)