Project Details


Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder. At this point in time, a diagnosis of ALS is coupled with little hope because there is no therapeutic intervention that will delay the course of the disease. Most patients with ALS die within 3-5 years of diagnosis. There are many factors that are thought to contribute to the loss of motor control that accompanies ALS, a major one of which is iron.

Iron and iron management is important in the brain, and there is a very sophisticated system in the body that maintains iron balance. This iron balance is vital, given that too little iron prevents cells from performing their normal functions effectively and efficiently, yet too much iron is detrimental because it can cause destruction of DNA, lipids, and proteins. A feature consistent with ALS pathology is iron deposition, and it is thought that this iron worsens ALS pathology and symptoms. The goal of our research is to determine if infusion of a protein that can bind and remove iron in a natural way is a potential treatment for amyotrophic lateral sclerosis. Specifically, our research investigates the use of apo-ferritin, ferritin that is not iron loaded, to sequester and redistribute the excess iron found in ALS, just as this protein already does in the brain in healthy patients. The concept is that ferritin will only bind up potentially toxic excess iron rather than sequestering it from proteins that need iron to function properly. Ferritin is known to travel from the brain to the cerebrospinal fluid and into the blood; it is this unique property of ferritin that makes it an attractive therapeutic agent, as iron from the brain will eventually be recycled elsewhere in the body where it is needed, for example, to make red blood cells.

Our grant proposal utilizes apo-ferritin infusion into the brain of mice that are genetically 'preprogrammed' to develop ALS motor symptoms and central nervous system pathology. We propose that this apo-ferritin treatment will slow or even prevent loss of motor control and extend lifespan by chelating and redistributing iron from the brain. We will also examine the contribution of a mutation in the gene for hemochromatosis that leads to iron overload in this ALS mouse model. Finally, we will determine if targeting a specific cell type, called microglia, with apo-ferritin is more beneficial than untargeted apo-ferritin. To do this, we will put apo-ferritin inside a tiny hollow bubble of lipids, called a liposome. With proper modifications and customization, this liposome targeting method in itself is revolutionary and could be used to deliver a number of different compounds to select cell populations in the brain.

If this research is successful, our apo-ferritin therapy could quickly transition to the clinic and be used in ALS patients within a few years because it is a natural compound and not a true 'drug.' The route of administration would be intrathecal infusion controlled by a pump, which simply means that apo-ferritin would be injected into the spinal canal -- a method similar to epidural anesthesia commonly used in childbirth. There is a very real possibility that apo-ferritin can extend the life and, equally importantly, improve quality of life by preserving motor function so that the brain and body work the way in which they were intended.

Effective start/end date1/1/10 → …


  • Congressionally Directed Medical Research Programs: $600,304.00


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