Use of bone marrow cells to deliver single chain antibodies in ALS

This project will use cells found in bone marrow as a potential means of delivering treatments to the diseased area in brain and spinal cord. One of the biggest hurdles in treating ALS is that even if something was developed to slow down or stop the disease, the brain and spinal cord are very difficult regions to access. Our bodies have a natural boundary to protect these areas called the blood-brain barrier that only permits certain substances (like oxygen and nutrients) to cross. In this way, it not only prevents many toxins and potentially harmful chemicals from entering these delicate regions, but also many drugs or potentially helpful chemicals. Most cells circulating in our bloodstream are unable to get past the blood-brain barrier, but Dr. Krieger’s team has determined that specific bone marrow cells are summoned to the brain and spinal cord during ALS progression and can cross through the blood-brain barrier. Using specialized laboratory techniques, Dr. Krieger’s group can remove these special cells from the bone marrow and give them capabilities that can provide treatment to the diseased area. By then transplanting them back into the bone marrow, they will be ready to deliver this treatment when called to the diseased site by the body. This Discovery Grant will examine the ability to provide these cells with specialized substances called nanobodies that can bind to and reduce levels of a toxic form of mutant superoxide dismutase (SOD1), which is known to cause ALS in a small percentage of hereditary cases and possibly affect sporadic cases as well. The technique will be attempted in mice and if successful, it will provide proof-of-principle for this novel delivery method. Such proof would then drive optimization of this protocol for delivery of SOD1 nanobodies or other potential treatments in humans.