April 6, 2006

Biotech Company Trophos Screening Finds Drug Candidate for ALS; Other Promising Treatment Avenues Reported at AAN

Researchers at a French biotech company presented animal findings on a new drug that could be promising for ALS. Reporting Thursday April 6 in San Diego at the meeting of the American Academy of Neurology, investigators at Trophos in Marseille, France showed that TRO19622 rescued lab-grown motor neurons from deprivation of growth factors, and in a mouse model of ALS increased survival, maintained weight and preserved motor function. The mice used in the experiments express a mutated version of the protein, copper-zinc superoxide dismutase (SOD1) and show many features of the human disease. Phase II/III testing of the drug are planned in the U.S. and in Europe for ALS patients this year.

Also reporting Thursday at the meeting, ALSA funded researchers at Drexel University in Philadelphia showed that a marker of inflammation is elevated in the mice that model ALS, adding to evidence that the disease involves inflammation that could be addressed through appropriate therapies. Terry D. Heiman-Patterson, M.D., and Timothy Cunningham, Ph.D., found that the secreted enzyme called phospholipase A2 (sPLA2) was increased in blood and urine of SOD1 mutant mice. Inhibitors are available for sPLA2 and could be tested in the mouse model of ALS.

Progress in finding biomarkers for earlier diagnosis and better clinical trials in ALS also was presented Thursday at AAN. Lisa Paige, Ph.D., of Metabolon, reporting for an ALSA-funded consortium, showed that 16 metabolic biomarkers and 19 protein biomarkers are altered in ALS. The metabolic biomarkers gave 83% sensitivity for identifying ALS patients. These predictive metabolites include alpha-aminoadipic acid, which is an intermediate in lysine degradation. Prior work on proteomic biomarkers has identified transthyretin, which functions in the vitamin A and protective metabolic pathways that produce the helper called glutathione. This proteomic panel identified ALS subjects with 80% sensitivity and 91% specificity. The consortium is working to further validate these markers in early stage ALS patients.

Meanwhile German investigators are making progress in the biomarker field for ALS. Johannes Brettschneider, M.D., working with Albert C. Ludolph, M.D., Hayrettin Tumani, M.D., and colleagues at the University of Ulm, Germany are findingbiomarkers for axonal degeneration in cerebrospinal fluid (CSF). Levels of a neurofilament marker in CSF were increased five fold, and tau was twice as high, in ALS patients compared to controls. The neurofilament marker was significantly higher in ALS than in patients with Alzheimer’s disease. The marker also showed promise in finding those with different sites of onset and those who progress more slowly.

To read more about ALS research at AAN, click here.