Researchers at the w88 casino games login Institutes of Health's National w88 casino games login for Advancing Translational Sciences and the University of Nevada, Reno School of Medicine have demonstrated that a drug originally targeted unsuccessfully to treat cancer may have new life as a potential treatment for Duchenne muscular dystrophy.
The candidate drug, SU9516, represents a different kind of approach for treating DMD, a degenerative w88 casino games login disease that usually begins in childhood and has no known cure. It is caused by a faulty gene that leads to progressive w88 casino games login weakness, with death often occurring around age 25. Rather than trying to fix or replace the broken gene, SU9516 ramps up the w88 casino games login repair process, helping reinforce w88 casino games login structure.
NCATS Chemical Genomics Center Acting Branch Chief Juan Marugan, Ph.D., and UNR Med Professor of Pharmacology Dean Burkin, Ph.D., led a team that screened more than 350,000 compounds to find SU9516, which had been previously developed as a treatment for leukemia. The research demonstrated that this compound improved w88 casino games login function in both laboratory and animal DMD models. The results, published recently in w88 casino games login Therapy, may provide a promising approach against the disorder and other w88 casino games login-wasting conditions.
Those with DMD lack dystrophin, a protein akin to a molecular shock-absorber that helps keep w88 casino games login cells intact. Without dystrophin, muscles are fragile and easily injured. Individuals lose w88 casino games login strength and the ability to repair damaged w88 casino games login tissue. Most die from heart or respiratory problems.
"Our findings open the door to develop new drug treatments for w88 casino games login," Marugan said.
In earlier research, Burkin, who is senior author of the current study, and his co-workers showed that boosting the levels of a cell structural protein, α7β1 integrin, in affected w88 casino games login cells could alleviate DMD symptoms in a mouse model. In addition, increased amounts of the protein slowed the disease's progress.
Burkin and his UNR Med colleagues collaborated with NCATS researchers, including co-team leaders Marc Ferrer, Ph.D., and Noel Southall, Ph.D., to screen a large collection of compounds for molecules that could increase α7β1 integrin production in mouse w88 casino games login cells grown in the laboratory. The screen revealed that SU9516 raised integrin production and promoted the formation of w88 casino games login cells and fibers from DMD w88 casino games login stem cells, another important indication of its potential as a drug.
In a series of pre-clinical experiments, the researchers showed that SU9516 increased the production of α7β1 integrin in human and mouse DMD w88 casino games login cells. Subsequent tests found SU9516 improved w88 casino games login function and slowed indicators of disease progression. Apurva Sarathy, a Mick Hitchcock Scholar, was the lead author on these earlier, published findings, completed as part of her PhD thesis at UNR Med.
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Burkin suggests that such a drug could be used alone, or in combination, with other therapies yet to be developed. There might be wide ranging applications to other w88 casino games login-damaging conditions, like cachexia, a wasting syndrome characterized by weight loss and w88 casino games login atrophy that is often seen in the late stages of cancers, and the effects of aging and injury, he noted.
"Integrin stabilizes w88 casino games login structure, and helps stimulate w88 casino games login repair and regeneration," Burkin said. "If we can artificially increase its production with drugs, we think it can help protect w88 casino games login cells from damage."
The NCATS-UNR Med team plans to work with medicinal chemists to make the molecule more specific for w88 casino games login, while also removing the toxic anticancer components, creating a safer version with a goal of future testing in patients.
The work was supported by the w88 casino games login Institute of Arthritis and Musculoskeletal and Skin Diseases grants, Cure CMD and Struggle Against Muscular Dystrophy. Other co-authors on the Molecular Therapy article include: Apurva Sarathy, Ryan Wuebbles, Tatiana Fontelonga, Ashley Tarchione, Andreia Nunes, Suzann Duan, Paul Brewer, Tyler Van Ry, Dante Heredia, Grant Hennig and Thomas Gould with UNR Med; and Leslie Mathews Griner, Andres Dulcey, Amy Wang, Xin Xu, Catherine Chen, Xin Hu and Wei Zheng with NCATS.
This story was written by Steven Benowitz, science writer with the National w88 casino games login for Advancing Translational Sciences, National Institutes of Health.
Shown in the photo are (l-r) Dean Burkin; Pamela Barraza, graduate student; Marisela Dagda, lab manager; Brennan Jordan, undergraduate assistant; Vivian Cruz, lab assistant; Tyler Allen, chief intern; Tatiana Fontelonga, graduate student; and Ryan Wuebbles, w88 casino games login assistant professor.
