PAAN/MIF Nuclease Inhibition for Neuroprotection in Multiple Sclerosis
Abstract
Multiple sclerosis (MS) is a major cause of progressive disability in young adults, including active military personnel and many Veterans, and there are no treatments that stop the chronic progressive form of the disease. Progressive MS is characterized by both loss of myelin (demyelination) and loss of the nerves and their extensions called axons. To date, several clinical trials have tested drugs for remyelination (wrapping new myelin around the nerve axons), but they have not resulted in improved function. This may, in part, reflect the fact that if the nerves are dead the axons are no longer available to be remyelinated. In addition, it is now recognized that the cells that make new myelin are also being killed. Herein, we propose to test a strategy to protect nerve cells (neurons) and myelin-making cells (oligodendrocytes) from being killed. We have identified a promising target that is seen in MS tissues (called MIF nuclease) and we can both eliminate that target genetically and use a new drug. We will test these in two different animal models of MS. One model (called EAE) allows us to look at nerve damage, and the second model (called AT-cuprizone) allows us to look at how the myelin-making cells die when attacked by immune system cells. We already have promising data from our neuroscience collaborators that inhibiting this cell death pathway works in other neurological diseases, and we have a drug that gets into the brain and treats a model of Parkinson s disease where there is also a lot of neuron damage. If successful, the data from the experiments proposed in this grant could lead to the development of a new kind of treatment for MS, which we think will be critical for protecting brain cells and repairing the damage to the myelin.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210819
Entities
People
- Peter Calabresi
Organizations
- Johns Hopkins University
- United States Army