Success Story

Oak Ridge Research to Aid in Treatment of Cardiovascular Disorders and Enhance Skeletal Muscle Regeneration

DrCymbeline teaser

Research conducted at Oak Ridge National Laboratory (ORNL) by Dr. Cymbeline T. Culiat based on a mutant mouse model indicates that the cell-signaling pathway based on the NELL1 (neural tissues containing epidermal growth factor-like domains) gene is critical to tissue growth and maturation in key mammalian organs.

NELL1 is a gene that codes for a cell-signaling protein that is critical for the formation and maturation of cardiovascular systems.

NELL1 triggers cell differentiation and growth via production of important factors (primarily extracellular matrix, cell adhesion and cell communication proteins) that are needed for the development of cardiomyocytes (heart muscle cells).

About 70% of the genes in the NELL1 pathway are critical in proper formation and function of the heart and blood vessels. Alterations in these genes (including NELL1) cause a variety of cardiovascular defects in humans and/or mice.

In the United States alone, 800,000 people per year suffer from a heart attack and 4.8 million are diagnosed with congestive heart failure.

Treatments for cardiovascular disorders based on the NELL1 protein or NELL1-secreting cells could repair and regenerate damaged cardiac muscle and blood vessels.

Direct delivery of the protein or cells to the site of treatment can occur using biological matrices, direct injection, catheter, and other delivery methods common to clinical treatments.

Furthermore, treatments for wound healing and myopathy based on the NELL1 protein or NELL1-secreting cells could repair and regenerate damaged skeletal muscle and blood vessels.

This opportunity has the potential of significantly improving human health by providing diagnostics and treatments for diseases that affect millions of people. Cardiovascular therapies with NELL1 can be utilized primarily for patients with damaged heart tissue resulting from heart attacks, congestive heart failure, and other cardiovascular disorders. The estimated potential market value is upwards of $3 billion.

Using genetic, genomic and molecular analyses of an ORNL mutant mouse model (NELL16R) generated from an earlier DOE-funded mutagenesis program, Dr. Culiat determined that the Nell1 protein stimulates the growth and maturation of cells/tissues in the musculoskeletal system such as bone, cartilage (Desai et al, 2006), cardiovascular and skeletal muscle systems (unpublished, 2007).

UT-Battelle, LLC (the contractor of ORNL) provided maturation funding support for Dr. Culiat to work on a commercial vision for this technology.

These key maturation projects completed the proof-of-concept studies needed to engage the commercial interest of a venture-funded startup, NellOne TherapeuticsTM, to pursue development of therapeutics that may one day provide critical medical treatments.

NellOne is an ORNL spinof that quickly began exploring the impact of Dr. Culiat’s research and sponsored work under a Work for Others at ORNL.

Today, Dr. Culiat is leading the NellOne TherapeuticsTM research effort to translate the NELL1 pathway discoveries into a therapy that restores both mass and function to damaged human tissues, such as heart and skeletal muscle.