Method to Inhibit Muscle Wasting

Description:

METHOD TO INHIBIT MUSCLE WASTING

 

Nilotinib  (TasignaTM) an off patent, FDA-approved kinase inhibitor has been used by UTHealth investigators at a significantly lower than approved dose as a treatment for muscle wasting. This suggests great potential as a therapeutic for syndromes such as cancer-associated cachexia and sarcopenia.

 

At 500 nM in vitro, it abrogates muscle catabolism without suppressing myogenesis mediated by p38β MAPK, and systemic administration of nilotinib at a low dose of 0.5 mg/kg/day alleviates muscle wasting and prolongs lifespan in tumor-bearing mice.

 

Background

Cachexia, characterized by muscle wasting, is a lethal metabolic syndrome without defined etiology and established treatment. Researchers at UTHealth previously found that p38β MAPK is essential for muscle wasting induced by circulating Hsp70/90 and inflammatory cytokines elevated in cancer, other inflammatory diseases and sarcopenia. As an effector of TLR4 and many cytokine receptors, p38β MAPK activates p300, C/EBPβ and ULK1 to stimulate muscle protein loss mediated by the ubiquitin-proteasome and autophagy-lysosome pathways.  Thus, p38β MAPK is a central mediator and therapeutic target of cancer and other inflammatory condition-induced muscle wasting.

 

Technology Highlights

•     Nilotinib, an FDA-approved kinase inhibitor that preferentially binds p38β        MAPK (Kd 32 nM) abrogates cancer-induced muscle catabolism at 500 nM in vitro:

•    ~20-fold more potent than the p38α/β MAPK inhibitor SB202190

•     without suppressing myogenesis mediated by p38a MAPK

•    Systemic administration of nilotinib in vivo at a low dose of 0.5 mg/kg/day               
alleviates muscle wasting and prolongs lifespan in tumor-bearing mice.

 

 

Intellectual Property Status

•     Patent pending

•     Available for licensing

 

Stage of Development

Preclinical

 

About the Investigator

Yi-Ping Li, Ph.D., is a Professor in the Department of Integrative Biology and Pharmacology at McGovern Medical School at UTHealth, Houston Texas. His research interests focus on signaling mechanisms of striated muscle remodeling.

 

Patent Information:

The preceding is intended to be a non-confidential and limited description of a novel technology created at the University of Texas Health Science Center at Houston (UTHealth). This promotional material is not comprehensive in scope and should not replace company’s diligence in a thorough evaluation of the technology. Please contact the Office of Technology Management for more information regarding this technology.
Category(s):
Therapeutics
For Information, Contact:
Yaya Lai
Technology License Associate
University of Texas Health Science Center At Houston
Chuan-Yar.Lai@uth.tmc.edu
Inventors:
Keywords:
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