Drug developers may soon have new drug targets for Lou Gehrig's disease, thanks to some promising studies of yeast. Details are highlighted in the journal Nature Genetics.
You may not expect yeast to have many human parallels, but scientists at the Stanford University School of Medicine and San Francisco's Gladstone Institutes were able to mimic the disease in baker's yeast by achieving higher-than-normal levels of expression of the RNA-binding protein TDP-43. Eventually, within the cells' cytoplasm, the protein bunched into deadly clumps, similar to how it advances in ALS patients. In humans with the neurodegenerative condition, TDP-43 builds up in clumps in parts of spinal cord neurons, the researchers explain. Patients with ALS also often have TDP-43 mutations.
With that in mind, the yeast experiments helped identify a possible drug target down the line for the disease also known as amyotrophic lateral sclerosis, or ALS. When they blocked production of the protein Dbr1, the TDP-43 clumps stopped forming and then lived as they normally would. Impressively, the researchers say, they duplicated the same results in human nerve cells cultured in the lab and also in rat neurons.
One promising test does not ensure a viable drug target, and it will be many years before this can be tested in humans. But the quest to develop a viable treatment for ALS continues, and drug developers are actively seeking new targets. Meanwhile, the researchers plan to seek out some possible small molecule inhibitors of Dbr1, and will test what happens when they block Dbr1 function in flies, worms and other rodents.
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