Study of the Safety and Efficacy of an Adeno-Associated Viral Vector Carrying the SMN Gene After a Single Intravenous Administration of Escalating Doses in Children With Spinal Muscular Atrophy (BLUEBELL)

Inclusion Criteria:

1. Informed consent form for participation in the study signed by the subject's legalrepresentative;
2. Subjects of either sex under the age of 240 days at the time of signing theInformation Sheet for the Legal Representative of the Clinical Study Subject withInformed Consent Form;
3. A diagnosis of 5q-SMA (homozygous deletion of exon 7 of the SMN1 gene or heterozygousdeletion of exon 7 + confirmed point mutation of the SMN1 gene) and 2 or 3 copies ofthe SMN2 gene established based on molecular genetic testing;
4. Subjects with 2 copies of the SMN2 gene can be included in the study both at thepresymptomatic stage of the disease and in the presence of SMA symptoms. If symptomsare present, the age of onset of the disease should be up to 180 days from birth.
5. Subjects with 3 copies of the SMN2 gene can be included in the study if they havesymptoms of SMA type 1 and the disease began before the age of 180 days.
6. The ability of the subject's legal representative, in the Investigator's opinion, toperceive information and follow the Protocol procedures

Exclusion Criteria:

1. A diagnosis of HIV infection, hepatitis B, hepatitis C, congenital syphilis in thestudy subject, as well as a documented diagnosis of HIV infection in the studysubject's mother. Note: documented hepatitis B and/or hepatitis C and/or syphilis inthe mother of a study subject is not an exclusion criterion in this clinical study,provided that standard breastfeeding rules are followed or the subject is notbreastfed due to the low risk of transmission of hepatitis B and C viruses andTreponema pallidum from mother to child with breast milk;
2. Unwillingness of the legal representative to use alternative feeding methods (nasogastric tube, gastrostomy) in case of swallowing disorders and a risk ofaspiration;
3. Anti-AAV9 antibody titer >1:50 determined by ELISA. Note: if a subject's screeninganti-AAV9 antibody titer is >1:50, the anti-AAV9 antibody titer may be determinedagain. Subjects with anti-AAV9 antibody titers ≤1:50 in the second test may beincluded in the study;
4. Need for respiratory support for ≥16 hours per day or tracheostomy ;
5. Treatment with nusinersen, risdiplam, branaplam, onasemnogene abeparvovec or otherantisense oligonucleotides/selective SMN2 splicing modifiers or gene therapy drugs forSMN1 transduction or other AAV-based gene therapy drugs regardless of serotype usedpreviously (from birth) or planned for the main study period, i.e., within 12 monthsafter the administration of the investigational product.
6. A need to use any medications for the treatment of myopathy or neuropathy, drugs forthe treatment of diabetes, ongoing immunosuppressive therapy, or the need forimmunosuppressive therapy after the start of the study (for example, glucocorticoids (except for premedication and post-medication), cyclosporine, tacrolimus,methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab, etc.);
7. Subjects with the following laboratory test results at screening:

• increased activity of transaminases (ALT, AST) or GGT >2×ULN;
• total bilirubin level ≥34 µmol/L;
• creatinine level ≥160 µmol/L;
• hemoglobin <80 g/L and >180 g/L;
• WBC count >20x109/L;
• Troponin I level > ULN.

8. Any concomitant diseases that, in the Investigator's opinion, may affect the safety ofANB-004 in the subject or have a significant impact on the assessment of the outcomesof SMA therapy;
9. A diagnosis of acute or chronic hepatic failure at screening;
10. A known allergy or intolerance to any components of the investigational product orpre- and post-medication drug (glucocorticoids);
11. Simultaneous participation of the subject in other clinical studies or previousparticipation in another clinical study using an experimental therapy.