Our Science

Industry-Leading Muscle Wasting Platform

Our research is grounded in understanding the role that α7β1 integrin and laminin play in muscle development and disease. We’ve built a drug discovery platform based on a novel screening system for integrin activators and we now have a robust IP including hundreds of scaffolds supporting thousands of compounds.

Extracellular Matrix (ECM)

The ECM acts as a scaffold for muscle cell migration, differentiation, and growth. The interaction between myocytes and ECM is facilitated by integrins, including α7β1 integrin, which links the cell surface to ECM components such as laminin.

Laminin

Laminin is a major component of the ECM and plays an important role in muscle development and disease. Laminin provides mechanical stability to muscle fibers and is involved in signaling pathways that regulate muscle differentiation, migration, and growth. In addition, laminin is important for maintaining the integrity of the basement membrane, which separates muscle fibers from connective tissue.

α7β1 Integrin

α7β1 integrin is a transmembrane protein that plays a role in the interaction between muscle cells (myocytes) and the extracellular matrix (ECM), which provides mechanical support to muscle fibers. The ECM also acts as a scaffold for muscle cell migration, differentiation, and growth. The interaction between myocytes and ECM is facilitated by integrins, including α7β1 integrin, which link the cell surface to ECM components such as laminin.

S-969

In collaboration with the National Chemical and Genomic Center at NIH, the Burkin Lab at University of Nevada Reno initially identified the compound S-969 as an enhancer of α7 integrin expression from the MLSMR library. S-969 is the lead of eight promising α7β1 integrin activators with indications for muscle wasting due to aging, chemotherapy, and muscular diseases, starting with Duchenne muscular dystrophy.

Sunitinib

The Food and Drug Administration (FDA)-approved small molecule, Sunitinib, is a potent α7 integrin enhancer capable of promoting myogenic regeneration by stimulating satellite cell activation and increasing myofiber fusion. Sunitinib exerts its regenerative effects via transient inhibition of SHP-2 and subsequent activation of the STAT3 pathway. We are investigating ultra-low-dose therapy to treat individuals living with muscular dystrophy.

LAM 111

Early-onset LAMA2-RD is the most common congenital muscular dystrophy affecting approximately 6,000 children in the U.S. and Europe and there are no approved therapies or ongoing clinical trials. Sarcomatrix is committed to developing Laminin-111, the embryonic form of laminin, as a protein replacement therapy for defective LAM-411/LAM-211 in individuals dealing with LAMA2-RD.

Putting It All Together

Dysregulation of α7β1 integrin and laminin function can contribute to muscle disease, including muscular dystrophy and other muscle wasting disorders. In these diseases, the normal interaction between muscle cells and the Extracellular Matrix (ECM) is disrupted, leading to muscle weakness, degeneration, and loss.

Thus, α7β1 integrin and laminin play crucial roles in muscle development and disease, and understanding their function and regulation is important for the development of therapeutic strategies for muscle disorders.

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