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Archive - Nov 7, 2019

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For First Time, Potential Treatment Path Becomes Clear for Subtype of Charcot-Marie-Tooth Disease

An unexpected finding from the Scripps Research laboratory of Xiang-Lei Yang (photo), PhD, has illuminated a potential strategy for treating the inherited neurological disease Charcot-Marie-Tooth (CMT), for which there is no approved medicine today. CMT is a progressive disease that typically develops early in life, affecting roughly 1 in 2,500 people. Over time, the disease inflicts damage on patients' peripheral nervous system--which extends from the spinal cord into the hands and feet--often resulting in difficulties with balance, walking, and fine motor skills such as writing or buttoning a shirt. In a study that was published online on November 6, 2019 in Nature Communications, Dr. Yang and her team show that a drug may be able to prevent the disease-causing mechanisms from occurring within cells, quelling many key symptoms, Including Motor Deficits. The open-access article is titled “Transcriptional Dysregulation by a Nucleus-Localized Aminoacyl-tRNA Synthetase Associated With Charcot-Marie-Tooth Neuropathy.” The approach centers on enzymes known as aminoacyl-tRNA synthetases (aaRSs), which are pervasive throughout the body. They are the largest protein family linked to CMT disease, and also the long-running research specialty of Dr. Yang's lab. These enzymes are essential to life because they kick off the first step of making new proteins, which are the building blocks of everything from blood and hormones to skin and bones. But in patients with CMT, some of the aaRS enzymes don't function as they should. As a result, peripheral neurons aren't made properly and become toxic to the peripheral nervous system. In her search for a potential treatment approach, Dr. Yang wanted to find out why the mutated enzymes only seem to affect peripheral neurons.

Researchers Seek to Attack Leukemia Stem Cells in Effort to Cure Chronic Myeloid Leukemia

Why do some cancers come back? Sometimes, a treatment can effectively eliminate cancer cells to undetectable levels, but, if the treatment stops, cancer may return. This is the case with chronic myeloid leukemia treated with drugs known as tyrosine kinase inhibitors. These drugs have dramatically improved clinical outcomes and generated unprecedented rates of complete responses and long-term survival. To achieve these results, patients have to take the drug for the rest of their lives. "Clinical trials testing the effect of discontinuing the drug have shown that at least half of the patients achieve treatment-free remission, but in the other half the cancer returns," said Daniel Lacorazza (photo), PhD, Associate Professor of Pathology & Immunology at Baylor College of Medicine and Principal Investigator in the Experimental Immunology & Hematology Laboratory at Texas Children's Hospital. "We think that relapse occurs because tyrosine kinase inhibitors affect most chronic myeloid leukemia cells, but not leukemia stem cells. It's like removing the tree, but leaving the roots that can sprout new shoots." Leukemia stem cells are an elusive, small cell population that initiates and sustains leukemia. Stem cells can regenerate via a poorly understood mechanism of self-renewal and enter a path of development that gives rise to new leukemia cells. Dr. Lacorazza and his colleagues think that clues to treatment-free remission might be found in this little known, self-renewal mechanism. "The results of the drug discontinuation trials suggest that a cure may not be possible with tyrosine kinase inhibitors alone.