PMID- 36324638
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221104
IS  - 2214-4269 (Print)
IS  - 2214-4269 (Electronic)
IS  - 2214-4269 (Linking)
VI  - 33
DP  - 2022 Dec
TI  - Treatment of CLN1 disease with a blood-brain barrier penetrating lysosomal 
      enzyme.
PG  - 100930
LID - 10.1016/j.ymgmr.2022.100930 [doi]
LID - 100930
AB  - Neuronal ceroid lipofuscinosis type 1(CLN1 disease) is a rare autosomal recessive 
      lysosomal storage disease caused by genetic defects of palmitoyl protein 
      thioesterase-1(PPT1), leading to accumulation of lipofuscin granules in brain and 
      progressive neurodegeneration. Psychomotor regression, seizures, loss of vision, 
      and movement disorder begin in infancy and result in early death. Currently, no 
      disease-modifying therapy is available. We report a 68-month-old boy with CLN1 
      treated on a compassionate use basis weekly for 26 months with a PPT1 enzyme 
      fused to an anti-insulin receptor antibody (AGT-194), thereby enabling 
      penetration of the blood-brain barrier (BBB). During treatment, no side effects 
      were observed, while seizure frequency decreased, life quality improved, and the 
      boy's general condition remained stable. This case documents for the first time 
      that treatment of CLN1 is principally feasible by an intravenous BBB penetrating 
      enzyme replacement therapy using PPT1 fused with the human insulin receptor. 
      Monitoring of side effects raised no unacceptable or unexpected safety 
      concerns.Observed improvement of life quality related to ameliorated epilepsy 
      control raises hope that further robust clinical trials including patients in 
      earlier stages of disease will show positive results.
CI  - (c) 2022 The Authors. Published by Elsevier Inc.
FAU - Hahn, Andreas
AU  - Hahn A
AD  - Department of Child Neurology, Justus-Liebig University Giessen, Germany.
FAU - Sato, Yuji
AU  - Sato Y
AD  - JCR Pharmaceuticals, Hyogo, Japan.
FAU - Ikeda, Toshiaki
AU  - Ikeda T
AD  - JCR Pharmaceuticals, Hyogo, Japan.
FAU - Sonoda, Hiroyuki
AU  - Sonoda H
AD  - JCR Pharmaceuticals, Hyogo, Japan.
FAU - Schmidt, Mathias
AU  - Schmidt M
AD  - JCR Pharmaceuticals, Hyogo, Japan.
FAU - Pfrimmer, Charlotte
AU  - Pfrimmer C
AD  - Department of Child Neurology, Justus-Liebig University Giessen, Germany.
FAU - Boado, Ruben J
AU  - Boado RJ
AD  - University of California, Los Angeles, USA.
FAU - Pardridge, William M
AU  - Pardridge WM
AD  - University of California, Los Angeles, USA.
LA  - eng
PT  - Case Reports
DEP - 20221026
PL  - United States
TA  - Mol Genet Metab Rep
JT  - Molecular genetics and metabolism reports
JID - 101624422
PMC - PMC9618832
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - CLN1 disease
OT  - Enzyme replacement therapy
OT  - Neuronal ceroid lipofuscinosis type 1
OT  - PPT1
COIS- AH and CP declare no competing interests. RB and WP are inventors of patents on 
      brain delivery of biologic drugs. YS, HS and MS are employees of JCR 
      Pharmaceuticals, the patent holder of AGT-194.
EDAT- 2022/11/04 06:00
MHDA- 2022/11/04 06:01
PMCR- 2022/10/26
CRDT- 2022/11/03 02:31
PHST- 2022/08/17 00:00 [received]
PHST- 2022/10/19 00:00 [revised]
PHST- 2022/10/21 00:00 [accepted]
PHST- 2022/11/03 02:31 [entrez]
PHST- 2022/11/04 06:00 [pubmed]
PHST- 2022/11/04 06:01 [medline]
PHST- 2022/10/26 00:00 [pmc-release]
AID - S2214-4269(22)00090-8 [pii]
AID - 100930 [pii]
AID - 10.1016/j.ymgmr.2022.100930 [doi]
PST - epublish
SO  - Mol Genet Metab Rep. 2022 Oct 26;33:100930. doi: 10.1016/j.ymgmr.2022.100930. 
      eCollection 2022 Dec.