Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis
Abstract
Iron accumulation and deposition have been reported in patients with amyotrophic lateral sclerosis (ALS). Previous work in mutant SOD1 mice mouse models of ALS have indicated that iron chelation with a chemical agent extends lifespan. Therefore, we propose the use of apo-ferritin, the iron-storage protein ferritin that is iron-poor, as a natural ionophore to sequester excess iron and redistribute it. The overall hypothesis is that infusion of apo-ferritin protein into the brain will provide neuroprotection by limiting the availability of excess iron to catalyze free-radical production. The most significant findings from this project are: 1.) Infusion of artificial cerebrospinal fluid (aCSF) containing nutrients, including H-ferritin, increases lifespan and delays onset of disease in SOD1G93A mice; 2.) This effect is not achieved by infusion of saline, suggesting that there is more than just a mechanical benefit to increasing flow of CSF 3;) In an accelerated disease model of ALS where mice carry both the HFEH67D allelic variant, present in 30% of ALS patients, and the SOD1G93A mutation, infusion of aCSF with or without H-ferritin is not beneficial. The high rate of oxidative stress in these animals may be too great for an infusion strategy; 4.) Infusion of H-ferritin protein encapsulated in liposomes is even more effective at delaying onset and extending lifespan than H-ferritin protein directly infused. The potential clinical significance of this work is that increasing turn-over of cerebrospinal fluid, and providing H-ferritin in a manner that may be more likely to be taken up by cells, appear to be viable therapeutic options for ALS patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2013
- Accession Number
- ADA588644
Entities
People
- James R. Connor
Organizations
- Pennsylvania State University