SCI TRANS MED: Clinical data show that brain AAV therapy saves babies from deadly genetic diseases

CLN2 disease, also known as late-stage infant neurolipid lignin deposition (LINCL), late-stage infant Batten disease, Janksy-Bielschowsky disease, and tripeptide peptidease 1 (TPP1) deficiency, is a deadly recessive neurodegenerative lysosome storage disorder in children caused by mutations in the CLN2 gene.
affects the central nervous system (CNS) and retina, the typical age of onset is 2 to 4 years old.
clinical process is characterized by aggressive neurodegeneration, accompanied by cognitive impairment, vision failure, seizures, deterioration of motor and language skills, and children generally die between the ages of 10 and 12.
the disease is caused by a mutation in the CLN2 gene that encodes the lysosome TPP1, an enzyme that degrades the peptide N end of the lysosome.
loss of TPP1 activity leads to the accumulation of stored substances in lysosomes, which are manifested under the photoscope as the accumulation of in-cell deposits with self-fluorescence.
recently, researchers tested intra-brain delivery of AAVrh.10hCLN2, a non-human serotoning rh.10 gland-related virus vector that encodes human CLN2, in a non-randomized trial consisting of two arms for an 18-month evaluation period.
trials included a queue of eight children with mild to moderate illness treated with AAVrh.10hCLN2, and an untreated Will Cornell natural history queue of 12 children.
the post-treatment queue was also compared with the European Natural History Queue for an untreated CLN2 disease.
, without immunosuppression, injects vectors directly into 12 parts of the brain through six burrs.
additional safety assessment under another program, five children with severe CLN2 disease were treated with AAVrh.10hCLN2.
therapy was associated with a variety of expected adverse events, none of which resulted in long-term disability.
the induced resistance to AAVrh.10 immunity is mild.
treatment, the cerebrospinal fluid TPP1 in the treatment queue increased by 1.3 to 2.6 times.
compared to the Weir-Cornell Natural History Queue (P<0.04) and the European Natural History Queue (P<0.0001), four of the seven children had slower gray mass loss and a decrease in motion and language function by 42.4 and 47.5 percent, respectively.
administration of AAVrh.10hCLN2 may delay the progression of the disease in children with CLN2.
, however, to use gene therapy to stop disease progress, we also need to improve vector design and delivery strategies.
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