Profiling Lipids in ALS

Free fatty acids (FFAs) circulate in blood to provide fuel for metabolism, to serve as substrates for the formation of more complex lipids, and to participate directly in biological signal transduction. Although these are easily detectable in blood, almost all are bound to albumin, a serum protein. When this happens, FFAs are unable to enter cells, bind to proteins, or serve as substrates for FFA-utilizing enzymes. Only soluble (unbound) FFAs are biologically active, and these soluble monomers represent just a tiny fraction of total FFAs. Because of this, measurements of total FFAs are insensitive to changes in the unbound (active) FFAs.  

To explore the role of fatty acids in the instance of neurodegenerative disorders, we have developed a collaboration with Membrane Sciences, a San Diego company founded by Dr. Alan Kleinfeld. The company has developed a highly sensitive means that allows for the measurement of unbound (and thus active) free fatty acids in biological fluids. In preliminary studies, we have found that approximately 40% of unbound free fatty acids are diminished in the plasma of ALS patients compared to normal subjects. To fully understand these findings and a possible alteration in several free fatty acids, we have obtained a large sample of plasma from patients whose clinical course has been monitored from their time of diagnosis. At the moment, we speculate that the alterations in fatty acids that have been observed in some patients are due to weight loss that commonly occurs during the disease. If confirmed, this information could potentially lead to a better understanding of ALS and its treatment.