Rapid Independent Evaluations of Lithium and Apocynin by ALS TDI


There have been many proposed therapeutics for ALS but a pair have garnered significant attention in the last half year: Lithium and Apocynin.  Lithium, typically associated with bi-polar disorder, was proposed as therapeutic in a publication from Italy which contained both human clinical data as well as results from testing in the mouse preclinical model of the disease.  ALS TDI researchers have examined the report closely and would be of the opinion, unfortunately, that flaws in the published human study preclude any determination of potential benefit for ALS in humans.  In a separate study, Apocynin, a natural compound that has been studied as potential drug in the past, was reported in a study from the University of Iowa to provide survival extension with dosage- and starting age- dependences.


Based on the prominence of these studies, and in the interest of bolstering support for proposed therapeutics in ALS, the Institute performed rapid re-evaluations in our independent lab.  ALS TDI runs the world's largest and most experience lab capable of evaluating drug benefit in the ALS mouse based on mutations in human SOD1.  Our pharmacology team contacted the Italian researchers to establish the exact dosage conditions for Lithium and, based on the information from the University of Iowa researchers, established dosage conditions for our tests that would have the potential to clearly indicate efficacy for Apocynin.  One study was performed for Lithium and two studies at different drug-initiation ages were initiated for Apocynin: all three studies are now completed and the data can be found by following the links at a thread on our Research and Treatments forum: http://www.als.net/forum/topic.asp?TOPIC_ID=2767


Our independent study of Lithium using the exact conditions reported by the Italian researchers indicated, unfortunately, no observable benefit for survival or muscle function in the ALS mouse.  Apocynin, on the other hand, has less straightforward conclusions at this point.  In contrast to the expectations based on the University of Iowa report, though, we did not see indications of strong efficacy in the mouse model.  However, we did observe a trend towards an extension of survival restricted only to the female mice.  Our researchers have already initiated a repeat of the earlier-starting age Apocynin study in the interest of increasing the number of animals studied which may allow a determination of statistical significance of the trend observed.


The research program at ALS TDI is designed to facilitate the successful identification of effective therapeutics in ALS patients during clinical trials.  The optimization of the chances that clinical trials will uncover efficacy requires having extensive, reliable data before the drug reaches the trial stage.  This need is why research at ALS TDI emphasizes high-powered studies in the animal model and a comprehensive biology discovery program to uncover all relevant therapeutic targets for new drug development.  In addition to studying these two compounds, ALS TDI has more than 40 other projects at varies stages of research at its state-of-the-art research facility in Cambridge, MA which hold promise for treating the disease.  To learn more about ALS TDI and to get the latest information about all of our work, please join us for a webinar on the third Thursday of each month.  You can register for an upcoming webinar by clicking here.