The goal of project PB002 is to develop a device that will improve clinical outcomes of plasmapheresis, a procedure of extracorporeal plasma filtration in NMO patients experiencing acute disease symptoms. The device, comprising an aptamer-functionalized selective adsorber, will precisely remove specific pathogenic compounds from the patient’s plasma, while returning all remaining non-pathogenic blood components to circulation. By doing so, this procedure will avoid adverse plasmapheresis-related complications, such as coagulation disorders and hemorrhage.
Neromyelitis Optica (NMO) is a rare orphan neurological disease with a paroxysmal, usually severe, and progressive course, in which the body’s autoimmune reaction generates self-recognizing antibodies (immunoglobulins), which attack the body’s own organs. This leads to inflammation of the spinal cord and optic nerves, resulting ultimately in their demyelination. Most patients experience a relapsing form of the disease, with periods of remission ranging from weeks to months. the disease can cause blindness via damage to the optic nerve, paresis or limb paralysis, and in extreme cases, respiratory and circulatory failure, leading to death. Despite that NMO disease is classified as a rare disease, it is estimated that nearly 300,000 people suffer from it globally.
Treatment options currently available to NMO patients include therapeutic plasma exchange, whereby their plasma is replaced by a replacement fluid, or immunoadsorption therapy, which either non-selectively or semi-selectively removes immunoglobulins from their blood. These therapies are associated with severe adverse effects, including coagulation disorders, hemorrhages or infection.
The PB002 product will exist in the form of a column to be used in selective adsorption – a therapeutic procedure whereby a patient’s plasma, after membrane or centrifuge-based separation from blood cells, passes through an adsorber, which selectively removes the pathogenic factors associated with NMO. This process occurs within the column, whereupon binding to ligands that are immobilized on the column matrix, pathogenic factors are removed from the patient’s plasma. Because of the highly specific nature of this process, other blood components should remain intact and returned to the patient’s circulation. In doing so, this novel form of therapy aims to achieve clinical improvement, while minimizing adverse outcomes that are associated with currently-used treatments.
The developed column will be based on aptamers – short single-stranded oligonucleotides that bind molecular targets with high affinity and specificity. Although aptamers recognize and bind targets in ways that are comparable to antibodies, they have a number of advantages, including shorter manufacturing times, lower costs of manufacturing, very low batch-to-batch variability, higher modifiability and better thermal stability. Aptamers specific to pathogenic NMO antibodies will be selected in Pure Biologics laboratories using the proprietary platform, PureApta.
Scientists at Pure Biologics have generated aptamers that are capable of highly selective capture of disease-causing molecules from human plasma. A method to immobilize the aptamer on an activated resin was also developed, facilitating its use in cartridges similar to those commonly employed in therapeutic plasmapheresis procedures. This resulting prototype was successfully tested in laboratory conditions. The next stage includes a safety and efficacy study, to be performed in an animal model during preclinical study, followed by examination of the device in patients suffering from NMO.
PROJECT DATA SHEET
Title: Development of the first in class therapeutic device for use in the treatment of autoimmune neurodegenerative disease
Program: Smart Growth Operational Programme 2014-2020
Value: PLN 14 281 990,88
Contribution of European Funds: PLN 10 541 538,16
Start: 1st June 2018
End: 31st May 2023