A research team led by Professors Yuan Zuyi, Wu Yue, and She Jianqing from the First Affiliated Hospital of Xi'an Jiaotong University (XJTU), in collaboration with Next Generation Gene Therapeutics Inc, recently achieved a clinical breakthrough in gene therapy for homozygous familial hypercholesterolemia (HoFH).

The clinical trial for their jointly developed gene therapy drug, NGGT006, yielded efficacy data, and the findings have been published in the international journal Nature Medicine.

HoFH is a life-threatening, severe hereditary metabolic disorder caused by genetic defects that strip the liver of its ability to clear low-density lipoprotein cholesterol (LDL-C) normally. Patients with HoFH have LDL-C levels four to nine times higher than healthy individuals.

Without effective intervention, most patients experience severe cardiovascular events or even sudden death before the age of 35, making clinical treatment exceptionally challenging. Current mainstream lipid-lowering drugs offer limited efficacy, while liver transplantation faces constraints such as donor shortages, high surgical risks, and the lifelong need for immunosuppressants. Consequently, a curative treatment has remained elusive globally, leaving a vast number of patients stranded in a therapeutic dilemma.

NGGT006 is an innovative gene therapy drug leveraging a recombinant adeno-associated virus (AAV8) vector. Delivered via a single intravenous infusion, the therapy introduces a functional human LDL receptor gene directly into the patient's hepatocytes.

By addressing the root cause, it repairs the liver's metabolic function and restores the body's capacity to clear LDL-C. The R&D team combined several technical strategies – including a hepatotropic vector, a liver-specific promoter, and codon optimization – to ensure safety while boosting the expression efficiency of the target protein.

While existing lipid-lowering methods like statins and PCSK9 inhibitors rely heavily on residual LDL receptor activity (rendering them largely ineffective for HoFH patients), and liver transplants remain heavily constrained by donor availability and long-term rejection risks, NGGT006 achieves three major breakthroughs: single-dose administration, long-term lipid control, and a root-cause cure. A single infusion achieved an LDL-C reduction of over 90 percent, with efficacy remaining stable throughout a 52-week follow-up period, opening a brand-new avenue for treating the disease.

This study marks the world's first gene therapy research for HoFH to enter the clinical stage with fully disclosed preclinical and human clinical trial data. It demonstrates for the first time that a single AAV gene therapy can effectively restore lipid metabolism in HoFH patients, delivering long-term, significant lipid-lowering results. This achievement not only fills a global technological gap in this field but also brings new hope to patients suffering from this rare disease.

Moving forward, the team will push ahead with multi-center, large-sample clinical trials and extended follow-up periods to further validate the long-term efficacy and safety of NGGT006.

Concurrently, the team will optimize dosage and immunosuppressive regimens to mitigate the risk of immune responses, striving to bring this original gene therapy to clinical fruition as early as possible for the benefit of rare disease patients worldwide.