EU-funded projects

PB005 AptaMG

Myasthenia gravis (MG) is an autoimmune condition classified as a rare disease. Accordingly, myasthenic patients lack effective treatment options, as this rare disease is not a primary interest of the pharmaceutical industry. However, considerable social and institutional support exists for the development of new therapies to treat rare diseases. The PB005 (AptaMG) project aims to develop a novel aptamer-based therapeutic medical device, to be used during an immunoadsorption procedure on patients experiencing myasthenic crisis, a life-threatening exacerbation of myasthenia symptoms.

OBJECTIVES

The goal is to develop a device that will improve clinical outcomes of plasmapheresis, a procedure of extracorporeal plasma filtration in patients experiencing a myasthenic crisis. The device, which will take the form of an aptamer-functionalized selective adsorber, will selectively remove pathogenic compounds from a patient’s plasma, while returning all other blood components back into circulation, thereby avoiding adverse effects associated with traditional plasmapheresis, such as hemorrhages and coagulation disorders.

DESCRIPTION

 

Myasthenia gravis (MG) is an autoimmune disorder caused by disrupted neurotransmission at  neuromuscular junctions. It is characterized by skeletal muscle weakness, leading to an increased susceptibility to fatigue. In most cases, MG is mediated by autoantibodies which bind to acetylcholine receptors, triggering an immune response and subsequent destruction of muscle membranes. Myasthenic crisis is a life-threatening complication of MG, characterized by worsening muscle weakness, resulting in respiratory failure that requires intubation and mechanical ventilation.

Treatment options currently available for myasthenic patients include therapeutic plasma exchange, whereby plasma is replaced with a replacement fluid; or immunoadsorption with a capacity to remove immunoglobulins. These non-selective or partially-selective therapies are associated with severe adverse effects, including hemorrhages, infections, and coagulation disorders.

Given the severe course which this disease can take, including motor impairment, respiratory failure, and possibly death, the solution proposed in the project responds to a highly unmet medical need. The PB005 product will take the form of a column to be used in a therapeutic procedure known as selective adsorption. During this procedure a patient’s plasma, after membrane- or centrifuge-based separation from blood cells, passes through an adsorber column where pathogenic factors associated with MG are specifically and selectively removed. This process occurs via binding the pathogenic factors to ligands immobilized on a matrix within the column. Other blood components should remain undisturbed and are returned to the patient’s circulation, thereby achieving clinical improvement, while minimizing adverse events associated with traditional treatment options.

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 comparably to antibodies, they have a number of advantages, including shorter generation time, lower costs of manufacturing, very low batch-to-batch variability, higher modifiability and better thermal stability. Myasthenia gravis-specific aptamers will be selected in Pure Biologics using its proprietary PureApta technology platform.

PROJECT PROGRESS

Three leading molecules were identified, and their sequences have been successfully truncated while maintaining strong and specific binding to the molecular target. High stability of these molecules in human plasma has also been demonstrated. Functional tests have begun that aim at development of the conditions of aptamers immobilization to the resin. We are also investigating the efficiency of target capture from plasma under static and dynamic conditions which will lead to the development of a column prototype.

PROJECT DATA SHEET

Title: Development of the first-in-class therapeutic medical device indicated to use during myasthenic crisis in myasthenia gravis patients
Program: Smart Growth Operational Programme 2014-2020
Value: PLN 14 733 265,56
Contribution of European Funds: PLN 10 775 212,49
Start: 1st March 2019
End: 30th September 2023

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Pure Biologics - Harnessing the power of antibodies and aptamers