$14M grants support rare metabolic genetics research

PHILADELPHIA— A $14M grant will support research into gene-editing therapies for rare metabolic diseases at the Perelman School of Medicine at the University of Pennsylvania (Penn) and the Children’s Hospital of Philadelphia (CHOP). The research will focus on developing treatments for urea cycle disorders, which affect about 1 in every 35,000 children. Using a type of CRISPR technology, the final vision of the four-year grant is to create a platform for the rapid development of gene therapy methods for a wide range of genetic disorders.

The grant, funded by the National Institutes of Health through its Somatic Cell Genome Editing (SCGE) Program, will support research to advance core editing, a new and revolutionary version of CRISPR technology. Unlike previous gene editing techniques, core editing allows precise changes to the genome, correcting any genetic change rather than simply changing chemical compounds. DNA strands. This technology holds promise for personalized therapy for patients with rare metabolic diseases such as type I citrullinemia, ASA lyase deficiency, and CPS1 deficiency. These life-threatening conditions, characterized by the body’s inability to break down proteins completely, often lead to toxic ammonia, which can cause brain damage, coma, or even death if left untreated.

Despite previous attempts to treat these diseases with gene therapy, success has been limited due to the immune response to modern therapy. Mainstreaming can change this by allowing permanent genetic modifications. “With this technology, we hope to not only control the symptoms, but provide a lasting, potentially life-long cure for these children,” said Kiran Musunuru, MD, PhD, professor of Cardiovascular Medicine. and Director of Genetic and Epigenetic Origins of the Penn Cardiovascular Institute. Disease Program.

“We’re not just focusing on one specific disease,” said Rebecca Ahrens-Nicklas, MD, PhD, attending physician with the Metabolic Disease Program and Division of Human Genetics at CHOP. “We’re focused on the patient in front of us, whatever condition they have. This method helps us to treat many patients who previously had no choice.”

The SCGE program is designed to deal with diseases caused by genetic mutations. In its first period (2018-2023), the program developed tools to perform genome editing in somatic cells, which are non-reproductive cells in the body. Now in its second phase, SCGE seeks to bring genome-editing therapies from the lab to the clinic.

The group, which previously received funding from SCGE, intends to start clinical trials within the next four years, marking an exciting new chapter in the field of precision medicine.