AAV‑Follistatin with optional VEGF plasmid to counter age-related muscle loss

Inclusion Criteria:

* Voluntary written informed consent obtained prior to any study-related procedures
* Ability to read, understand, and sign the Informed Consent Form and reliably complete required study documents
* Willingness to undergo medical intervention, including genetic therapy, and to comply with the visit schedule and all study procedures
* Commitment to maintain a stable medication and supplement regimen throughout the study, with no initiation of new medications, supplements, or performance-enhancing substances unless approved by the Investigator
* Men and women aged 35-75 years
* Body mass index (BMI) between 18.0 and 35.0 kg/m² at screening
* Active Prospera ZEDE eResidency or Physical Residency
* Stable comorbid conditions for at least 3 months prior to screening
* Postmenopausal status (women)
* Willingness to use reliable contraception for 6 months following therapy
* Low or undetectable antibody titers to AAV9 (≤1:100 by ELISA)

Exclusion Criteria:

* Pregnancy, breastfeeding, or intent to become pregnant; premenopausal status (unless ≥12 months amenorrhea or FSH ≥30 IU/L)
* Subjects who have a history of alcohol or drug abuse within 1 year of study entry
* Initiation of prohibited medications, supplements, or interventions during the study period that may confound efficacy or safety assessments
* Active malignancy or ANY history of cancer
* Strong family history of cancer in first-degree relatives (≥2 relatives with cancer diagnosed \<60 years) OR known hereditary cancer syndrome (BRCA1/2, Lynch syndrome, Li-Fraumeni, FAP, HNPCC) without genetic counseling and enhanced surveillance clearance
* Clinically significant cardiovascular disease, including:
* Any history of stroke, transient ischemic attack (TIA), myocardial infarction (MI), or unstable angina (regardless of time since event)
* Diagnosed coronary artery disease (CAD) documented by coronary angiography or stress testing
* Significant atherosclerotic disease at any location (stenosis ≥50% in carotid, femoral, or other major arteries)
* Prior coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\])
* Prior valvular repair or replacement
* History or current diagnosis of heart failure
* Uncontrolled hypertension (SBP \>140 mmHg or DBP \>85 mmHg despite treatment)
* Left ventricular ejection fraction (LVEF) \<50%, QTc ≥480 ms, or severe valvular heart disease
* Ventricular arrhythmias requiring chronic drug treatment or implantable cardioverter-defibrillator
* Presence of pacemaker or persistent left bundle branch block (LBBB)
* Known diagnosed cardiomyopathy of any etiology
* Significant left ventricular hypertrophy, defined as maximal left ventricular wall thickness ≥15 mm in any segment at end-diastole (by echocardiography or cardiac MRI)
* Known or suspected hypercoagulable state/thrombophilia, including any of the following:
* Any history of venous thromboembolism (DVT, PE, or thrombosis at any site), particularly if:
* Unprovoked, or
* Associated with only minor provoking factors (e.g., minor surgery, combined oral contraceptives, short-term immobilization)
* Recurrent thrombotic events, including recurrent superficial venous thrombosis
* Thrombosis at unusual sites, including but not limited to:
* Mesenteric, portal, or splenic vein thrombosis
* Cerebral venous sinus thrombosis
* Hepatic vein thrombosis (Budd-Chiari syndrome)
* Renal vein thrombosis
* Retinal vein thrombosis
* Superior vena cava thrombosis not related to central venous catheterization
* Strong family history of venous or arterial thrombosis at a young age in first-degree relatives
* History of recurrent pregnancy loss or severe obstetric complications suggestive of a hypercoagulable state
* High-degree myopia (≥ -6.0 diopters) or pathological myopia without ophthalmologic clearance
* Any history of retinal detachment, vitreous hemorrhage, or retinal vascular disease (diabetic retinopathy, retinal vein occlusion, age-related macular degeneration with neovascularization)
* Use of systemic anti-VEGF therapy (e.g., bevacizumab)
* Current use of prohibited medications or supplements (see Section 4.3)
* Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL) at screening
* HbA1c ≥6.5% (≥48 mmol/mol) at screening
* Current diabetes mellitus (any type)
* History of peptic ulcer disease within 12 months
* Known osteoporosis (DXA T-score ≤ -2.5 at the hip or spine)
* Severe pulmonary disease, including COPD or restrictive lung disease (FVC \<49% predicted)
* Advanced renal disease (CKD stage 3-5, eGFR \<60 mL/min/1.73 m²) or dialysis dependence
* Chronic liver disease or hepatic impairment:
* Any history of cirrhosis, chronic viral hepatitis (HBV, HCV), autoimmune hepatitis, or cholestatic liver disease
* Active hepatitis or evidence of hepatic decompensation
* ALT or AST \>1.5× upper limit of normal (ULN)
* Total bilirubin \>1.5× ULN (unless due to Gilbert's syndrome)
* Non-alcoholic steatohepatitis (NASH) and clinically significant liver fibrosis
* Active cholecystitis, symptomatic gallbladder disease (e.g., biliary colic), or any other clinically significant hepatobiliary abnormality
* Neurodegenerative, neuromuscular, psychiatric, or movement disorders associated with functional or cognitive impairment (e.g., dementia, Parkinson's disease)
* History of drug-induced myopathy or rhabdomyolysis
* Elevated creatine kinase (CK) at screening CK \>1.0× ULN confirmed on two separate occasions at least 48 hours apart
* Exception: Transient CK elevation within 72 hours of strenuous exercise, intramuscular injections, or trauma is permitted if CK normalizes (≤1.0× ULN) on repeat testing before baseline visit
* Systemic connective tissue diseases (CTDs), including:
* Systemic lupus erythematosus (SLE), SLE overlap syndromes, or drug-induced SLE
* Mixed connective tissue disease (MCTD)
* Systemic sclerosis (SSc, scleroderma): diffuse, limited, or sine scleroderma
* Inflammatory myopathies: polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), immune-mediated necrotizing myopathy (IMNM), or overlap myositis
* Primary Sjögren's syndrome requiring systemic immunosuppression (corticosteroids \>10 mg/day prednisone equivalent, DMARDs, or biologics)
* Rheumatoid arthritis with extra-articular manifestations or requiring biologic DMARDs
* Undifferentiated connective tissue disease (UCTD) meeting ≥2 CTD classification criteria
* Current or recent (within 3 months) use of immunosuppressive agents, including corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IVIG, or rituximab
* Acute bacterial, fungal, or viral infection, fever, or receipt of live vaccines within 30 days prior to screening
* Infectious disease exclusions, including:
* Active hepatitis B infection or reactivation risk (HBsAg positive, HBV DNA detectable, or isolated anti-HBc without anti-HBs)
* Hepatitis C infection (detectable HCV RNA or treatment within 6 months)
* HIV infection
* Active or latent tuberculosis (positive QuantiFERON-TB Gold Plus ≥0.35 IU/mL)
* Acute herpesvirus infection, defined as
* Active HSV-1 or HSV-2 lesions (vesicles, ulcers, crusts) on clinical examination at screening
* CMV or EBV IgM positive
* Increased bleeding risk, including platelet count \<100 ×10⁹/L, active anticoagulation (unless washout possible), or known coagulation disorders
* Severe physical functional limitation (CFS\>6)
* Prior exposure to any AAV gene therapy product (any AAV serotype)
* Prior exposure to any investigational drug within 90 days
* Participation in another clinical trial within 90 days
* Known hypersensitivity to investigational product components or immunosuppressive agents (e.g., prednisone, rapamycin)
* Life expectancy \<6 months
* Any condition that, in the Investigator's judgment, may pose undue risk, interfere with study outcomes, or impair study participation