Open Label Study for the Use of Plasmapheresis for Treatment of Age-Related Frailty

As population aging continues to accelerate around the world, there is increasing recognition of health burdens related to frailty. Age-related frailty indisputably reduces quality of life for an aging-individual, as well as for caregiving individuals. To date, there is no proven effective therapy or cure for age-related frailty. There is an urgent need to address the burden of frailty with possible therapeutic solutions.

One model proposed nine hallmarks of aging which fall into three categories: 1) primary causes of cellular damage (e.g., genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis); 2) compensatory or antagonistic responses to damage (e.g., deregulated nutrient sensing; mitochondrial dysfunction, cellular senescence); and 3) the integrative result of (1) and (2) that is considered responsible for functional decline (e.g., stem cell exhaustion, altered intercellular communication). In more recent reports, frailty has been defined as a syndrome related to the fatigue of physiological systems; in other words, it is "a state of increased vulnerability to poor resolution of homeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homeostatic reserves until minor stressor events trigger disproportionate changes in health status". This definition of frailty as a syndrome whose incidence increases with aging is based on research that highlights its relationship with various biological processes rather than chronological age.

It has been proposed that an underlying mechanism leading to many frailty-related neurological diseases is a gradual build up of certain molecules in patients' plasma. Molecules such as auto-antibodies develop naturally over time in response to disease over a patient's life span, but build up of these molecules has been linked to both central and peripheral nervous system disorders such as Alzheimer's and Parkinsons. Specifically, beta-amyloid accumulation and toxic autoimmunity-related proteins have been used as markers of aging-related neurological diseases such as Alzheimer's Disease (AD) and multiple sclerosis (MS). Considering this, a successful treatment for many neurological disorders including those listed has been the process of Plasmapheresis. In Plasmapheresis, the process is to extract some of a patient's blood, remove a percentage of the plasma in the blood, and finally replace it with either 1) donor plasma, 2) albumin, or 3) a combination of saline with albumin. This process ultimately dilutes the amount of harmful molecules. The American Society for Apheresis (ASFA) has determined that Plasmapheresis is accepted as a Category 1 (or first-line therapy) for nervous system disorders that exhibit frailty symptoms such as: Acute Inflammatory Demyelinating Polyneuropathy (Guillain-Barre Syndrome), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), Multiple Sclerosis (MS), and more.

Studies have suggested low serum hypoalbuminemia (albumin) is a significant risk factor for frailty in elderly patients. Therefore, a possible treatment approach for age-related frailty is to not only remove the build up of harmful molecules with plasmapheresis, but to replenish serum albumin during reinfusion. A recent study demonstrated that utilizing albumin in plasmapheresis decreased concentration of Amyloid-Beta plaque build up in cerebrospinal fluid, as well as increased scores on cognitive, functional, and behavioral tests in elderly patients with Alzheimer's Disease. The present study is therefore designed to assess clinical benefit of plasmapheresis with albumin in patients with age related frailty.

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