Conference Coverage

Plasma exchange is ‘encouraging’ as a novel Alzheimer’s disease treatment



Plasma exchange with albumin replacement may be effective for slowing down symptoms of Alzheimer’s disease, new research suggests. Results from the phase 2b/3 AMBAR study showed that the treatment, which aims to remove amyloid-beta (Abeta) from plasma, was associated with a 60% decrease in functional and cognitive decline in patients with moderate Alzheimer’s disease.

The reduction in cognitive decline uncovered by the study is more striking than that reported for other investigational treatments targeting Abeta, such as monoclonal antibodies, said coinvestigator Antonio Páez, MD, medical director of the AMBAR program, Alzheimer’s Research Group, Grifols, Barcelona.

The results “open a new path for the development of plasma protein replacement therapies not only in Alzheimer’s disease but also in other degenerative diseases that we are planning to investigate,” Dr. Páez said.

The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were simultaneously published in Alzheimer’s and Dementia.

Removing amyloid

Plasma exchange treatments, which have been available for several decades, are used to treat a range of neurologic, immunologic, and metabolic disorders. The treatment involves plasmapheresis, whereby plasma is separated from blood cells (red blood cells, white blood cells, platelets, etc) and toxic substances are removed. The albumin in plasma, to which plasma Abeta is bound, is replaced with a fresh commercial albumin product made from plasma from healthy donors.

“Our initial hypothesis was that, by removing albumin together with Abeta and substituting it with newer albumin periodically, we may be removing Abeta from the cerebrospinal fluid and eventually from the brain,” Dr. Páez said.

The AMBAR study included 347 men and women aged 55-85 years with probable Alzheimer’s disease dementia who were enrolled at 41 sites in Spain and the United States. All were diagnosed with mild Alzheimer’s disease, as shown by a baseline Mini-Mental State Examination score of 22-26, or moderate Alzheimer’s disease, having a baseline MMSE score of 18-21.

Investigators randomly assigned the participants to four groups; one group received placebo, and each of the other three treatment arms received different doses of albumin and intravenous immunoglobulin (IVIg) replacement.

During the first 6-week study phase, patients received weekly sham or conventional plasma exchange treatments of 2.5-3 liters of plasma, which Dr. Páez referred to as the “intensive-treatment phase to remove as much Abeta as possible.”

This was followed by a 12-month maintenance phase, which involved monthly low-volume (700-800 mL) plasma exchange or sham treatments.

Although the volume of plasma removed was the same in all three active-treatment groups, the amount of albumin and IVIg that was subsequently replaced varied. In one group, the same amount of albumin and IVIg that was removed was replaced; in another, half the amount removed was replaced; and in the third, only albumin was replaced.

The researchers collected cerebrospinal fluid (CSF) samples at baseline and after each treatment period. They assessed Abeta40, Abeta42, total tau, and phosphorylated-tau biomarkers.

The two primary outcomes were change from baseline to 14 months in scores on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog).


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