University College London, United Kingdom
Term: 7/1/21 – 6/30/22
The gradual accumulation of disability during progressive MS is mainly due to the loss of nerve cells (neurons) in the brain and spinal cord, but why they die is not known. One question is whether the neurons that die later in life do so because of damaging events happening at that time, or as the aftermath of earlier injury. This question is important because protecting neurons from ongoing inflammation is likely to require a different approach than protecting neurons that have survived this event, and now need repairing. The team is approaching this question with a rodent model using a new technique that allows the simultaneous detection of thousands of instructions from the cell’s control center (nuclei) that reveal pathways of damage. The team has already found that preventing an oxygen shortage that occurs within inflamed MS lesions may protect from slow degeneration. They will protect half of the rodents using this therapy, and compare the changes in injured cells in untreated rodents whose neurons are destined to slowly die, with changes in cells that have experienced the same inflammation, but survive. This will reveal specific mechanisms that determine cell death or survival, without confusing them with changes due to inflammation itself.
This research is expected to provide clues to the development of therapies to prevent nerve degeneration in people with secondary progressive MS. This expert team plans to build on the new understanding to test the efficacy of potential therapies based on the new findings.
The gradual accumulation of disability during progressive MS is mainly due to the loss of nerve cells (neurons) in the brain and spinal cord, but why they die is not known. One question is whether the neurons that die later in life do so because of damaging events happening at that time, or as the aftermath of earlier injury. This question is important because protecting neurons from ongoing inflammation is likely to require a different approach than protecting neurons that have survived this event, and now need repairing. The team is approaching this question with a rodent model using a new technique that allows the simultaneous detection of thousands of instructions from the cell’s control center (nuclei) that reveal pathways of damage. The team has already found that preventing an oxygen shortage that occurs within inflamed MS lesions may protect from slow degeneration. They will protect half of the rodents using this therapy, and compare the changes in injured cells in untreated rodents whose neurons are destined to slowly die, with changes in cells that have experienced the same inflammation, but survive. This will reveal specific mechanisms that determine cell death or survival, without confusing them with changes due to inflammation itself.
This research is expected to provide clues to the development of therapies to prevent nerve degeneration in people with secondary progressive MS. This expert team plans to build on the new understanding to test the efficacy of potential therapies based on the new findings.