The cell and gene therapy company’s lead in vivo candidate uses lentiviral vector delivery to correct metabolic disorder in large animal model of hereditary tyrosinemia type-1
EXTON, Pennsylvania – August 30, 2022 – Castle Creek Biosciences announced publication of a preclinical study that found that its experimental in vivo gene therapy treatment resolved biochemical and hepatic histological markers of hereditary tyrosinemia type-1 (HT1) in a large animal model of the disease. The findings appear in the August 25 edition of Nature Communications.
Researchers at Mayo Clinic administered a therapeutic lentiviral vector designed to integrate a functional human fumarylacetoacetate hydrolase (FAH) transgene into the liver of the pig model of HT1. The direct in vivo delivery of a single intraportal dose of the vector carrying the human FAH gene normalized liver function 78-98 days post-treatment, according to the published study.
“This preclinical research demonstrated that lentiviral vector gene therapy was active in a large animal model of HT1 and the pigs did not experience adverse events from the integrating vector,” said senior author Joseph Lillegard, MD, PhD, Castle Creek Biosciences chief scientific officer. “We saw a complete resolution of the biochemical and histologic features of tyrosinemia in the liver and demonstrated the benign integration pattern of the vector into the pig genome.”
“Interestingly, at 12-months post-treatment, the liver was repopulated with healthy, FAH-positive hepatocytes,” said co-author Stephen J. Russell, MD, PhD, of the Mayo Clinic Comprehensive Cancer Center. “This latest finding builds on a six-year series of preclinical studies that we hope will lead to an initial clinical trial in patients with HT1.”
Hereditary tyrosinemia type-1 (HT1) is an autosomal recessive inborn error of metabolism characterized by the inability to completely metabolize tyrosine. Caused by a deficiency of the terminal enzyme of the pathway, FAH, HT1 causes an accumulation of toxic metabolites in the liver resulting in severe oxidative damage.
Patients who are untreated commonly experience high rates of fibrosis, cirrhosis, liver failure and hepatocellular carcinoma (HCC) at a very young age. Patients with HT1 are currently treated with medication that reduces the toxic metabolites responsible for liver disease progression.
Editor’s Note: Funding for this study came from Children’s Hospitals of Minnesota, with additional support provided by Regenerative Medicine Minnesota. Castle Creek Biosciences provided no financial support for the study.
About Castle Creek Biosciences, Inc.
Castle Creek Biosciences is a late-stage cell and gene therapy company developing treatments for skin, connective tissue and metabolic diseases. Founded by Paragon Biosciences, Castle Creek’s pipeline uses cutting-edge technologies that create optimal therapies for a broad range of genetic diseases. For more information, visit https://castlecreekbio.com/
About Paragon Biosciences, LLC
Paragon Biosciences is a global life science leader that creates and builds innovative biology-based companies in three key areas: cell and gene therapy, adaptive biology and advanced biotechnology. Our portfolio companies use biology to accelerate scientific breakthroughs that solve some of society’s most challenging problems. Committed to this goal, Paragon and its partners have invested more than $1.4 billion in its portfolio companies since 2017. Learn more at https://paragonbiosci.com/.
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