Clinical Study of LY-M001 Injection in the Treatment of Adolescents With Type I Gaucher Disease

Inclusion Criteria:

1. The subject and/or parent, caregiver, or legal representative must be willing andable to provide written informed consent/consent for the study in accordance withapplicable regulations and guidelines and comply with all study access andprocedures, including the use of any data collection devices that can be used todirectly record participant data;

2. Gender is not limited, 12 years old ≤ 18 years old;

3. Patients with double allele mutation of glucocerebrosidase gene (GBA1) and decreasedglucocerebrosidase activity were confirmed by laboratory tests and met the clinicalmanifestations of type I Gaucher disease;

4. Subjects were newly treated or treated patients with type I Gaucher disease; Forpatients treated with enzyme replacement therapy (ERT) or substrate clearancetherapy (SRT) before screening, 5 drug half-lives are required beforeadministration;

5. The subject is willing to participate in all study follow-up and comply with allstudy procedures and evaluations;

6. The subject must be willing to refrain from donating blood, organs, tissues, orcells at any time after receiving treatment;

7. Pregnant Women (WOCBP) subjects tested negative for pregnancy. Note: WOCBP isdefined as a female subject who has not achieved postmenopausal status (continuousamenorrhea for at least 12 months with no clear cause other than menopause) aftermenstruating, and who has no surgical (i.e., bilateral ovariectomy, fallopian tuberemoval, and/or hysterectomy) or other investigator identified cause of permanentinfertility (e.g., mallear tube agenesis).

Exclusion Criteria:

1. Positive AAV8 neutralizing antibody (antibody titer > 1:10).

2. Patients with type II or III Gaucher disease (GD2 or GD3), or with suspected Gaucherdisease as assessed by the investigator (e.g., subjects with Gaucher disease-relatedcentral nervous system manifestations or abnormal electroencephalogram [EEG]examination).

3. Active and progressive bone diseases that are expected to require surgical treatmentwithin the next 6 months.

4. The subjects were judged by the investigator to have idiopathic thrombocytopenicpurpura (ITP), thrombotic thrombocytopenic purpura (TTP), thrombocytopenia, anemia,hepatomeglia, splenomeglia, and/or osteoporosis unrelated to GD (bone mineraldensity z-score ±2).

5. Treatment with an investigational drug in another clinical study within 28 daysprior to screening or 5 half-lives, whichever is older.

6. Evidence of a history of clinically significant liver disease or hepatotoxinexposure that meets, but is not limited to, any of the following at the time ofscreening:

① Progressive hepatomegaly larger than 3 times the normal volume

② History of stage 2 or above hepatic fibrosis

③AST, ALT, or TBIL were 1.5 times higher than the upper limit of normal (ULN)

④ Immune hepatitis Hepatitis B surface antigen (HBsAg) positive, and hepatitis Bvirus deoxyribonucleic acid (HBV-DNA) positive (HBV-DNA>103 copy number /mL); Ortake hepatitis B drugs (such as interferon, lamivudine, adefovir and entecavir); Orhepatitis C virus (HCV) antibody positive.

7. The subject's blood indicators have any of the following:

① The hemoglobin value was <8.0 g/dL

② Platelet count <40 × 109/L

8. Refractory epilepsy.

9. Human immunodeficiency virus (HIV) antibody positive or treponema syphilis antibodypositive.

10. Subjects had significant clinical comorbidities (such as malignant tumors, primarybiliary cirrhosis, or autoimmune liver disease) that the investigators believedmight affect the study data or confounding the findings.

11. Subjects have received or plan to receive bone marrow transplantation, hematopoieticstem cell transplantation, and/or major organ transplantation, including but notlimited to liver transplantation, kidney transplantation, etc.

12. 3 months before screening, subjects received treatment with erythropoietin, wholeblood transfusion, or red blood cell transfusion; Or received platelet transfusion 1month before screening.

13. Allergic to any component of LY-M001 injection.

14. Previous treatment with any type of gene therapy or cell therapy.

15. Use of systemic immunosuppressant or steroid therapy within 3 months prior toadministration (other than immunosuppressive therapy prescribed for prophylacticadministration).

16. Any condition in which the subject is unable to undergo magnetic resonance imaging (MRI) studies (including hypersensitivity to anesthetics or contrast agents).

17. Have received live attenuated vaccine within 4 months prior to screening or plan toreceive live attenuated vaccine during clinical trials.

18. Other situations in which the investigator considers the subject inappropriate forstudy participation.