Commencing January 2025, Dr Aakanksha Dixit, working with Co-applicant A/Prof Judith Greer, was awarded a 2-year Translational Research Project Grant, the title being, “An aptamer-based approach to therapy of multiple sclerosis” at the University of Queensland.
The underlying reason for the development of symptoms of MS is that a material called myelin that coats the nerve cells is broken down (demyelination). During the early stages of MS, most people will recover after an attack, due to repair of the damaged myelin in a process called remyelination. As time goes on, however, the recovery process fails, and the amount of disability that is experienced by people with MS (PwMS) can increase. Also, accompanying this failure of recovery, PwMS can develop irreparable damage to the nerve cells in the brain and spinal cord (neurodegeneration). Scientists need to better understand what causes failure of remyelination and neurodegeneration (remembering that these causes might not be identical in everyone).
Previously, Dr Dixit and A/Prof Greer have identified some proteins (called PLP-specific antibodies) that are present in the blood and cerebrospinal fluid of about 50% of PwMS—these can cause demyelination, failure of remyelination and neurodegeneration in brain cell cultures and in animal models of MS. Dr Dixit proposes that by specifically removing these proteins, they could improve recovery after an attack and enhance the long-term outcomes. To do this, the aim of this project is to make and test novel therapeutic agents known as aptamers and test their ability to remove and/or block the action of the PLP-specific antibodies.
In the first year of the project, Dr Dixit and her team have been making the aptamers. The first step was to prepare highly purified preparations of the PLP-specific antibodies (that they want the aptamers to be able to remove) from the blood of 10 PwMS. They have also prepared highly purified antibodies that aren’t specific for PLP (and therefore not able to cause the type of damage seen in MS) from 10 healthy individuals. Both of these are then used in a selection process to “pull out”, from an initial “library” of over 100 trillion aptamers, the small number (~50) that will bind very specifically to the PLP-specific antibodies. In the final year, Dr Dixit and A/Prof Greer will now use the selected aptamers to test their ability to remove and block the action of the antibodies from serum and CSF of PwMS. Results will be prepared for submission as a manuscript.