A major step forward in the quest to develop real treatments for amyotrophic lateral sclerosis, ALS, or Lou Gehrig's disease has come to fruition. The report is a culmination of a series of studies begun by Harvard Stem Cell Institute (HSCI) scientists eight years ago.
The findings by Harvard professor of Stem Cell and Regenerative Biology (HSCRB) Kevin Eggan and colleagues also has produced functionally identical results in human motor neurons in a laboratory dish and in a mouse model of the disease, demonstrating that the modeling of human disease with customized stem cells in the laboratory could someday relatively soon eliminate some of the need for animal testing.
The new study, published today in Science Translational Medicine, suggest that compounds already in clinical trials for other purposes may be promising candidate therapeutics for ALS. The Harvard authors found that genetically intervening in the pathway these drugs act on increased survival time of an ALS animal model 5-10 percent, and while that is a long way from curing the universally fatal neurodegenerative disease, "any ALS patient would be excited about this extended life span," said Eggan, who pioneered the disease in a dish concept.
They further report that when the effected receptor is blocked, the ALS damage done by the glial cells is reduced. This latest work, says Eggan, first done in human motor neurons in a dish, and then in a mouse model of ALS, "says that indeed this stem cell model was predictive of something that can happen inside a whole animal, and its important because it demonstrates that this is really an important target for an ALS therapeutic. If we can inhibit this receptor in an ALS patient, we might slow down the progression of the disease, and that would be a huge step." Eggan said "one feature of the glial cells in ALS that attack motor neurons is that they have higher expression of this prostanoid receptor. Removing just one of the two copies of the receptor in the glial cells had an effect on extending the life span" of the ALS mice," Eggan said, and "inhibition by a drug is unlikely to have an effect as complete as a knockout in the mice. "Eggan said that experiments on human stem cell-generated ALS motor neurons also show that " if we inhibit that receptor in the ALS cells with a chemical, those cells lose their toxicity to motor neurons "This is a very exciting period for those whose lives are threatened by ALS, and it is exciting for my lab," Eggan said. "First we recently identified a pathway that we think is important for degeneration inside the motor neuron, and now we've found this pathway in cells outside the motor neuron. This has potential to have a very substantial effect on what's happening in ALS." The research was funded by Project ALS, the New York Stem Cell Foundation, P2ALS, and the Howard Hughes Medical Institute.