Rheological treatment methods and related apheresis systems

Abstract

Therapeutic apheresis treatments and diagnostic monitoring methods are described, specifically relating to the depletion and / or removal of a broad bandwidth of certain rheologically active elements from the blood of a patient followed by return of the blood so treated to the patient, and to methods or procedures of apheresis treatment, especially biophysiologic blood filtering treatments and computer medicated delivery methods configured to provide such apheresis treatments to patients with certain chronic, age-related, degenerative, atherogenic, thrombotic or inflammatory diseases; especially those associated with RAM accumulation-deposition causing disturbances of blood rheology or microcirculatory impairment.

Description

RELATED CASES [0001] This application is based on U.S. Provisional Application Ser. No. 60 / 114,144, filed Dec. 29, 1998 and U.S. Provisional Application Ser. No. 60 / 158,049, filed Oct. 7, 1999, these applications being hereby incorporated by reference in their entirety.FIELD OF THE INVENTION [0002] The invention relates generally to the treatment of various disorders caused by or associated with relatively elevated levels of certain high molecular weight blood plasma components, particularly those rheologically active macromolecules that generally are larger than about 500,000 Daltons (500 kDa) in weight or greater than about 200 Å in diameter. Elevated levels of such plasma constituents are found in chronic, age-related, degenerative, and / or inflammatory diseases associated with the accumulation of and / or deposition of biological substances that result in or are associated with disturbances of blood rheology, extra-cellular matrix composition, and intrinsic endothelial cell functio...

AI Technical Summary

Benefits of technology

[0055] It is contemplated that such therapeutic methods will be effective to produce in the patient one or more responses, such as: (1) increased microperfusion or capillary function; (2) improved immune response; or (3) extraction of tissue-bound RAM and to deplete the extracted RAM from the patient's plasma. Such methods generally will be effective to produce in the patient a clinically observable improvement in a disorder characterized by elevated plasma levels of rheologically active macromolecules. Such disorders include: (1) age-related macular degeneration; (2) atherosclerosis; (3) rheumatoid arthritis; (4) autoimmune diseases; (5) Diabetes; (6) Alzheimer's disease; (7) Procoagulant states, and (8) neurodegenerative diseases.

Problems solved by technology

(3) disrupt numerous intrinsic endothelial cell functions, and (4) cause numerous other pathologies which can promote various disturbances in the microcirculation.

Any prolonged disruption of this delicate balance of promoters and inhibitors can lead to a pathologic deterioration of the clinical state into conditions that ultimately manifest themselves as disease.

For example, chronically ill patients are typically significantly older than patients with acute conditions, often have significant co-morbidities (heart disease, etc.), consume numerous medications, and in general are typically less robust (resilient) than the younger acute patient group.

Accordingly, the use of apheresis to treat such chronically ill patients has been relatively limited.

The reported genetic defect in AMD renders this waste removal pipeline less effective, allowing accumulations of debris to collect in the posterior retina at the layer of the RPE / Bruch's complex.

It is believed that these deposits are directly toxic to surrounding retinal tissues, and that they may play a role in the progression of AMD.

Current research attempts to improve patients' vision by laser applications to these drusen deposits have been disappointing.

Therefore, until now, other than laser photocoagulation, there has been no therapy widely recognized to be effective and therefore commonly recommended for the treatment of this disease, and most certainly in its early “dry” stages.

These prior studies, however, failed to optimize timing intervals associated with apheresis treatments and therefore were unable to demonstrate maximal improvement in clinical outcomes.

Specifically, the AMD study utilized a monthly interval between individual apheresis treatment cycles of two session which was insufficient to maintain reduced levels of RAMs.

The apheresis treatment protocol was also considered to be unsatisfactory because of the extended period of time prior to treatment (six hours).

This mandate represents the fundamental challenge of vascular disease management at present, especially given the time-to-effective-treatment requirements.

However, the high costs and technical complexities associated with these methods have precluded them thus far as widely accepted options in those markets currently addressed by pharmaceutical and dietary interventions.

However, the principle reason for the lack of general acceptance is that the technologies are considerably too specific (removing LDL almost exclusively) to be of substantial benefit in moderating the majority of the mechanisms associated with acute vascular injury response / reperfusion damage.

However, the current overhead expense of the hospital environment adds significant costs to these procedures that need not necessarily be applied to apheresis treatments for relatively clinically stable yet chronically ill patients.

Similarly, most patients with such diseases are not aware that they have a condition potentially treatable with the apheresis methods described herein or that such a potentially beneficial apheresis treatment option exists in such out-patient settings.

This form of apheresis is more complicated and more expensive than Rheopheresis® blood filtration as described herein.

These settings remain unmodified for the specific needs of these patients.

In Europe, out-patient LDL apheresis clinics are used specifically for lipid lowering in select hyperlipidemic patients, however, these facilities are not designed to moderate rheologic diseases, nor are they disease specific clinics.

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