PRECISION MEDICINE PLATFORM
Dilated cardiomyopathy, in which the heart becomes dilated and the muscle walls become thin, is a major cause of heart failure hospitalizations and death and the most common reason for heart transplantation. About 25 to 50 percent of dilated cardiomyopathy is inherited, and an estimated 1 in 2,500 to 3,000 people are affected with GDCM, although the true extent of the disease may be larger. No current therapies are targeted to GDCM or for specific mutations, and none prevent decline in asymptomatic patients.
GENE THERAPY PLATFORM
CELLULAR REGENERATION PLATFORM
In patients who have had a myocardial infarction (MI), the affected part of the heart is no longer functional due primarily to loss of cardiomyocytes. As cardiomyocytes do not divide, a regenerative approach is needed to replace lost cardiomyocytes and restore cardiac function.
Cardiac fibroblasts are the most abundant cell type in the heart, comprising up to 50 percent of cardiac cells following a MI. These cells represent a reprogrammable pool of cells residing at the site of the injury.
Our cardiomyopathy drug discovery platform is based on advances in the genetics of FDCM, which has been linked to more than 50 genes, and includes two approaches:
Tenaya has created isogenic human induced pluripotent stem cell (iPSC)-derived cardiomyocytes with specific mutations as disease models for GDCM. These iPSC-derived cardiomyocytes are used to identify and validate heart failure targets and drive high-throughput screening for therapeutic compounds.
Tenaya has created iPSC-derived cardiomyocytes from individuals with DCM and is using these patient-derived cells to determine the applicability of targets identified from screens in GDCM iPSCs to the broader DCM patient population.
Tenaya’s unique approach identifies potentially novel targets acting downstream of multiple DCM genotypes, providing the opportunity to address causes of heart failure that may have relevance to broader populations as well.
Tenaya has developed in-house capabilities to develop viral vectors to deliver and selectively express genetic payloads in specific cell types in the heart.
Tenaya has established robust early in-house AAV manufacturing capabilities including upstream and downstream process development and analytical development.
Current projects are focused on severe genetically defined cardiomyopathies, with the potential to expand to more prevalent cardiac conditions.
Tenaya’s approach involves in vivo reprogramming of resident cardiac fibroblasts into cardiomyocytes. Tenaya uses novel AAV vectors to introduce proprietary combinations of known transcription factors – genes that control cellular identity and function – to convert cardiac fibroblasts into cardiomyocytes. This can help repair the heart, reduce the scar area, and improve heart function.
Tenaya’s initial focus is on developing disease modifying treatments for MI and for disorders involving cardiac fibrosis and cardiomyocyte loss.