Gaucher disease (GD) is caused by mutations in the GBA1 gene, which leads to a lack or reduction of GCase activity. The consequences of this deficiency are generally attributed to the accumulation of the GCase substrate, Glucosylceramide (GlcCer), in macrophages in the liver, spleen, kidney, bone, lung, and even the brain, inducing their transformation into Gaucher cells whose cell cytoplasm presenting a characteristic "crumpled tissue paper" appearance, leading to pathological changes in involved tissues and organs.LY-M001 Injection is an rAAV8 vector gene therapy product. It can specifically transduce the target organ liver after a single intravenous administration and express the GCase protein in liver cells for a long period of time.
Age ≥ 18 years and ≤ 60 years, male or female.
The subjects should fully understand the purpose, nature, and method of this study as well as possible adverse reactions, and sign the informed consent form (ICF) voluntarily.
Patients with confirmed double mutations in the GBA1 allele through laboratory testing, and the glucocerebrosidase activity was reduced to less than 30% of the normal value(For example, the result of the dried blood spot (DBS) method is < 1.19 μmol/L/h), and meeting the standard clinical diagnosis criteria for GD1.
Treated patients with Gaucher disease type I who had previously received enzyme replacement therapy (ERT) or substrate clearance therapy (SRT) with GD, were on stable medication, eluted 5 drugs for a half-life or more before administration, or were comprehensively judged to be stable by the investigator.
AAV8 neutralizing antibody positive (Antibody titer > 1:40).
Patients with clinically diagnosed Gaucher disease type II or III (GD2 or GD3).
Active and progressive bone disease that is expected to require surgical treatment within the next 6 months.
Subject has idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), thrombocytopenia, anemia, hepatomegaly, splenomegaly, and/or osteoporosis unrelated to GD as judged by the Investigator.
Single group
LY-M001
GeneticSingle Intravenous Infusion of LY-M001 Injection.
Phase I: Incidence of adverse events (AE) and serious adverse events (SAE) within 52 weeks after LY-M001 infusion
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Phase I: Incidence rate of dose-limiting toxicity (DLT) events determined by the data safety review committee (SRC) within at least 28 days after LY-M001 infusion.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.The adverse events defined as dose-limiting toxicity (DLT) have been clearly specified in the protocol.
Phase I: Liver function levels (including alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin [TBIL], alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT]) within 52 weeks after LY-M001 infusion.
Incidence rate of liver function-related adverse events evaluated by CTCAE V5.0.
Phase II: Blood glucocerebrosidase (GCase) activity level.
Evaluation based on the detected values of blood glucocerebrosidase（GCase).
Phase I: Liver volume and spleen volume (if applicable)
1. Change from baseline in liver volume as measured by MRI through 52 weeks after infusion of LY-M001; 2. Change from baseline in spleen volume as measured by MRI through 52 weeks after infusion of LY-M001.
Phase I: Hemoglobin levels
Evaluate the change from baseline in hemoglobin levels through 52 weeks after infusion of LY-M001.
Phase I:Bone mineral density (BMD) after administration
Evaluate the change from baseline in bone mineral density (BMD) by dual-energy X-ray absorptiometry through 52 weeks after infusion of LY-M001.
Phase I: Glucocerebrosidase (GCase) protein levels in blood
Evaluate the change from baseline in GCase protein levels through 52 weeks after infusion of LY-M001.
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