A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)

Inclusion criteria

• Male and female subjects aged 18 and 65 years with clinical diagnosis of LGMD2I/R9 and confirmation of FKRP gene mutation.
• Ability to walk/run 10 meters in <30 seconds.
• Able to understand and comply with all study procedures.
• Sexually active females of childbearing potential and female and male partners of male subjects receiving study intervention must use a barrier method of contraception for the first 6 months after dosing.

Exclusion criteria

• Significant cardiomyopathy as defined by echocardiogram (left ventricular ejection fraction <40%), evidence of conduction defect (increased PR and RR intervals, left bundle branch block and QTcF >480m/sec), NYHA Class 3 or 4 heart failure, or MRI gadolinium enhancement evidence of clinically important myocardial fibrosis.
• Contraindication to MRI or hypersensitivity to contrast dyes, shellfish or iodine.
• Implanted spinal rods, cardiac pacemaker or other implantation that would distort cardiac MRI images.
• History of active, ongoing chronic liver disease (e.g. hepatitis, HIV-related liver disease, hemochromatosis, steatosis, etc.) or abnormal liver function tests (abnormal GGT and/or abnormal total/direct bilirubin >upper limit of normal [ULN] and/or elevated AST and ALT >2 ULN).
• Abnormal renal function (GFR <60 ml/min, using the Modification of Diet in Renal Disease equation).
• Any life-threatening disease, including malignant neoplasms and medical history or malignant neoplasms within the past 5 years prior to screening (except basal and squamous cell skin cancer).
• In the opinion of the investigator, a pre-existing medical condition that predisposes the subject to risks that outweighs the potential benefits.
• Requirement for daytime ventilatory support.
• Change in glucocorticosteroid treatment within 3 months prior to screening visit.
• Exposure to another investigational drug within 3 months prior to study treatment or any previous treatment with gene therapy.
• Ongoing participation in any other therapeutic clinical trial.
• Neutralizing antibody titer to AAV9 >1:5.
• Female subjects who are pregnant, plan to become pregnant in the next 12 months, or breastfeeding.