This study is a single-center, single-arm, non-randomized, open-label, non controlled, dose-escalation, prospective clinical trial designed to assess the safety, tolerability, and preliminary efficacy of JWK008 injection in patients with MPS I.
MPS I is a rare autosomal recessive disease caused by deficiency of the α-L-iduronidase (IDUA) gene, which encodes a lysosomal enzyme required for degradation of glycosaminoglycans (GAGs).While currently available therapies, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), provide clinical benefit over untreated disease progression,they still have significant limitations. ERT does not cross the blood-brain barrier and, therefore, does not treat the central nervous system (CNS) effects of the disease. And HSCT, although it can prevent cognitive decline in patients, has a high mortality rate and morbidity. The investigators have designed a novel IDUA fusion protein with the ability to cross the blood-brain barrier through the addition of the brain-targeting peptide Mtfp. On this basis, the investigators constructed an IDUA gene expression cassette for liver-targeted expression, and used a highly efficient liver-specific promoter to make the IDUA gene specifically and efficiently expressed in liver tissue, and the expressed protein can enter the central nervous system to exert therapeutic effects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Six participants with MPS I will be enrolled in the study. The participantss will be divided into two different dose groups, and a "3+3" dose escalation design is used. The low dose is 5.0×10\^12vg/kg, and the high dose is 2.0×10\^13vg/kg. Only one intravenous infusion of JWK008 will be administered to each participant.
West China Hospital, Sichuan Universit
Chengdu, Sichuan, China
RECRUITINGadverse events
Adverse events defined as the number of participants with adverse events according CTCAE 5.0
Time frame: 5 years
IDUA enzyme activity in blood and cerebrospinal fluid
Changes in IDUA activity in blood and cerebrospinal fluid before and after treatment are detected by laboratory testing.
Time frame: 5 years
GAG levels in blood, urine, and cerebrospinal fluid
Changes in GAG levels in blood, urine, and cerebrospinal fluid before and after treatment are detected by laboratory testing.
Time frame: 5 years
Six-Minute Walk Test
The distance that the patient could withstand the fastest walking distance on flat ground within 6 minutes before and after treatment was measured
Time frame: 5 years
Range of the joint motion(JROM) testing by measuring ruler
A measuring ruler was used to detect changes in the participant's range of the joint motion before and after treatment
Time frame: 5 years
Liver and spleen size were detected by CT
Changes in liver and spleen size were detected by CT
Time frame: 5 years
Vector shedding
As measured by vector concentration (quantitative polymerase chain reaction to JWK008 deoxyribonucleic acid ) in CSF, serum, and urine
Time frame: 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.