Cell and gene therapy company’s lead in vivo candidate uses delivery of lentiviral vectors to correct metabolic disorders in a large animal model hereditary tyrosinemia type 1
EXTON, Pa., August 30, 2022 /PRNewswire/ — Castle Creek Biosciences announced the publication of a preclinical study which revealed that its experimental properties live 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 Communication.
Mayo Clinic researchers administered a therapeutic lentiviral vector designed to integrate a functional human fumarylacetoacetate hydrolase (FAH) transgene into the liver of the porcine model of HT1. The direct live administration of a single intraportal dose of the vector carrying the human FAH gene normalized liver function 78 to 98 days after 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 that pigs did not experience adverse effects from the integrating vector,” said the lead author. Joseph Lillegard, MD, PhD, Scientific Director of Castle Creek Biosciences. “We saw complete resolution of the biochemical and histological features of tyrosinemia in the liver and demonstrated the pattern of benign vector integration into the pig genome.”
“Interestingly, 12 months after treatment, the liver was repopulated with healthy, FAH-positive hepatocytes,” the co-author said. Stephen J.Russell, MD, PhD, from the Mayo Clinic Comprehensive Cancer Center. “This latest finding builds on a six-year series of preclinical studies that we hope will lead to a first clinical trial in patients with HT1.”
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive inborn error of metabolism characterized by the inability to fully metabolize tyrosine. Caused by a deficiency in 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 not treated usually have high rates of fibrosis, cirrhosis, liver failure and hepatocellular carcinoma (HCC) at a very young age. Patients with HT1 are currently treated with drugs that reduce the toxic metabolites responsible for the progression of liver disease.
Editor’s Note: Funding for this study comes from Children’s Hospitals in 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 advanced technologies that create optimal therapies for a wide range of genetic diseases. For more information visit https://castlecreekbio.com/
About Paragon Biosciences, LLC
Paragon Biosciences is a global life sciences 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 toughest problems. Committed to this goal, Paragon and its partners have invested over $1.4 billion in its portfolio companies since 2017. Learn more at https://paragonbiosci.com/.
SOURCECastle Creek Biosciences