Novel compound seen to ease heart muscle disease in FA models
Stealth's SBT-589 also shows protective effects against cell energy deficits
Stealth Biotherapeutics’ investigational therapy SBT-589 showed protective effects against cell energy deficits and heart muscle disease across several preclinical models of Friedreich’s ataxia (FA), including a mouse model of pronounced heart disease, according to new laboratory data.
SBT-589 is designed to boost the activity of mitochondria — known as the powerhouses of cells — whose function is impaired in FA, especially in heart muscle cells. As a result, FA patients develop cardiomyopathy, or heart muscle disease, for which no approved therapies are available.
The data were presented by Laura E. Kropp, PhD, Stealth’s senior manager of discovery biology, at the Wellcome Trust Conference on Mitochondrial Medicine – Therapeutic Development, which took place March 18-20 in the U.K.
“The new findings … support continued development of SBT-589 as a potentially disease-modifying therapy to address the unmet need in cardiomyopathy associated with Friedreich’s ataxia,” David A. Brown, senior vice president of discovery at Stealth, said in a company press release. That release calls SBT-589 “a promising novel molecule.”
Heart muscle disease in FA ranks among leading causes of death
FA is caused by mutations in the FXN gene, which lead to defective production of frataxin, an essential protein for the normal functioning of mitochondria. Dysfunctional mitochondria cannot provide the required energy to high-demanding cells, including those in the nervous system and heart muscle.
“Mitochondrial dysfunction is a central contributor to … Friedreich’s ataxia, a disease in which heart failure and sudden cardiac events are among the leading causes of mortality,” Brown said.
“Mitigating heart disease in FA is central to Stealth’s ongoing efforts to improve the lives of individuals with FA,” Brown added.
In three distinct preclinical models, a team of scientists assessed the protective potential of SBT-589. One was a model of lab-grown FA patient-derived cells, while another was of isolated heart mitochondria. The third was a mouse model of FA-related heart disease. This mouse model shows symptoms of pronounced heart enlargement or cardiac hypertrophy, and early death.
Mitigating heart disease in FA is central to Stealth’s ongoing efforts to improve the lives of individuals with FA.
The results showed that SBT-589 protected against mitochondrial damage and boosted energy production across all of the models. Compared with mice given a sham solution, animals treated with SBT-589 once a day showed a significant reduction in cardiac hypertrophy and a delayed death, the data showed.
According to Stealth, further preclinical studies are underway to continue to assess the therapeutic potential of the treatment candidate, and are “expected to build on these insights as SBT-589 progresses through developmental stage-gates.”
The results will be used to support a potential application to test SBT-589 in human clinical trials, the company says.
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