Details of Disease

General Information of Disease (ID: DISZC5YB)

• Disease Name: CLN2 Batten disease
• Synonyms: neuronal ceroid lipofuscinosis, juvenile; ceroid lipofuscinosis, neuronal, 3; Vogt-Spielmeyer disease; Spielmeyer-Sjogren disease; Vogt Spielmeyer disease; batten disease; CLN3 disease; CLN3 disease, juvenile; Spielmeyer Sjogren disease; CLN3; neuronal ceroid lipofuscinosis 3; ceroid lipofuscinosis, neuronal, type 3; neuronal ceroid lipofuscinosis caused by mutation in CLN3; Juvenile CLN3 Disease; CLN3 neuronal ceroid lipofuscinosis; neuronal ceroid lipofuscinosis type 3
• Disease Class: 5C56: Lysosomal disease
• Definition: A condition associated with mutation(s) in the CLN3 gene, encoding battenin. The condition is one of a group of genetically heterogeneous neurodegenerative disorders, characterized by accumulation of intracellular lipopigments.
• Disease Hierarchy:
  DISX9A5W: Juvenile neuronal ceroid lipofuscinosis
  DIS9A4K4: Neuronal ceroid lipofuscinosis
  DISZC5YB: CLN2 Batten disease
• ICD Code: ICD-11: ICD-11: 5C56
• Disease Identifiers:
  MONDO ID: MONDO_0008767
  MESH ID: D009472
  UMLS CUI: C0751383
  OMIM ID: 204200
  MedGen ID: 155549
  Orphanet ID: 228346
  SNOMED CT ID: 61663001

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
LX1004	DMKRZ0R	Phase 1/2	Gene therapy	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CLCN3	TT8XNZ7	Limited	Biomarker	[2]
CLCN6	TTCJRDO	Limited	Biomarker	[3]
CLN6	TTJCOQ7	Strong	Biomarker	[4]
CTSD	TTPT2QI	Strong	Genetic Variation	[5]
GAD2	TT7UY6K	Strong	Biomarker	[6]
NCL	TTK1V5Q	Strong	Biomarker	[7]
TPP1	TTOVYPT	Strong	Biomarker	[8]
TRIP10	TTKHTGE	Strong	Biomarker	[9]
CLN3	TTORF9W	Definitive	Autosomal recessive	[10]
PPT1	TTSQC14	Definitive	Altered Expression	[11]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SULT1A1	DEYWLRK	Strong	Biomarker	[9]
SULT1A3	DEP7E8X	Strong	Biomarker	[9]

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CAPN3	OTCHG3YK	Limited	Biomarker	[12]
CAPN8	OTXTW2I4	Limited	Biomarker	[12]
CLN5	OTY265P6	moderate	Biomarker	[13]
ACP2	OTLPA1LJ	Strong	Biomarker	[14]
ATP13A2	OTKWBUGK	Strong	Biomarker	[15]
ATP5F1E	OTMPLAIS	Strong	Biomarker	[16]
ATP5MC1	OTOLSYOI	Strong	Genetic Variation	[17]
CLN8	OT0D4CB5	Strong	Genetic Variation	[18]
EPM2A	OTJU4IAG	Strong	Genetic Variation	[19]
ERG	OTOTX9VU	Strong	Biomarker	[20]
HOOK1	OTTTKV7V	Strong	Biomarker	[21]
KCNIP3	OTCQPEM4	Strong	Genetic Variation	[22]
MFSD8	OT455EIC	Strong	Genetic Variation	[23]
POTEF	OTV3WXYE	Strong	Biomarker	[24]
SULT1A4	OTHJ8WWV	Strong	Biomarker	[9]
CLN3	OTDDKT8R	Definitive	Autosomal recessive	[10]

References

• [1] Clinical pipeline report, company report or official report of Lexeo Therapeutics
• [2] ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation.J Biol Chem. 2005 Jan 14;280(2):1241-7. doi: 10.1074/jbc.M407030200. Epub 2004 Oct 25.
• [3] Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13854-9. doi: 10.1073/pnas.0606137103. Epub 2006 Sep 1.
• [4] Tracking sex-dependent differences in a mouse model of CLN6-Batten disease.Orphanet J Rare Dis. 2019 Jan 21;14(1):19. doi: 10.1186/s13023-019-0994-8.
• [5] Cathepsin D deficiency and NCL/Batten disease: there's more to death than apoptosis.Autophagy. 2007 Sep-Oct;3(5):474-6. doi: 10.4161/auto.4341. Epub 2007 Apr 25.
• [6] IgG entry and deposition are components of the neuroimmune response in Batten disease.Neurobiol Dis. 2007 Feb;25(2):239-51. doi: 10.1016/j.nbd.2006.09.005. Epub 2006 Oct 27.
• [7] Flunarizine rescues reduced lifespan in CLN3 triple knock-out Caenorhabditis elegans model of batten disease.J Inherit Metab Dis. 2017 Mar;40(2):291-296. doi: 10.1007/s10545-016-9986-1. Epub 2016 Oct 20.
• [8] Therapeutic landscape for Batten disease: current treatments and future prospects.Nat Rev Neurol. 2019 Mar;15(3):161-178. doi: 10.1038/s41582-019-0138-8.
• [9] Analysis of Batten disease candidate genes STP and STM.Am J Med Genet. 1995 Jun 5;57(2):324-6. doi: 10.1002/ajmg.1320570244.
• [10] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [11] Cln3-mutations underlying juvenile neuronal ceroid lipofuscinosis cause significantly reduced levels of Palmitoyl-protein thioesterases-1 (Ppt1)-protein and Ppt1-enzyme activity in the lysosome.J Inherit Metab Dis. 2019 Sep;42(5):944-954. doi: 10.1002/jimd.12106. Epub 2019 May 14.
• [12] Batten disease: biochemical and molecular characterization revealing novel PPT1 and TPP1 gene mutations in Indian patients.BMC Neurol. 2018 Dec 12;18(1):203. doi: 10.1186/s12883-018-1206-1.
• [13] Longitudinal InVivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease.Mol Ther. 2018 Oct 3;26(10):2366-2378. doi: 10.1016/j.ymthe.2018.07.015. Epub 2018 Jul 17.
• [14] Increased expression of lysosomal acid phosphatase in CLN3-defective cells and mouse brain tissue.J Neurochem. 2007 Dec;103(6):2177-88. doi: 10.1111/j.1471-4159.2007.04920.x. Epub 2007 Sep 11.
• [15] Characterization of cellular protective effects of ATP13A2/PARK9 expression and alterations resulting from pathogenic mutants. J Neurosci Res. 2012 Dec;90(12):2306-16. doi: 10.1002/jnr.23112. Epub 2012 Jul 30.
• [16] An Autophagy Modifier Screen Identifies Small Molecules Capable of Reducing Autophagosome Accumulation in a Model of CLN3-Mediated Neurodegeneration.Cells. 2019 Nov 27;8(12):1531. doi: 10.3390/cells8121531.
• [17] Distinct early molecular responses to mutations causing vLINCL and JNCL presage ATP synthase subunit C accumulation in cerebellar cells.PLoS One. 2011 Feb 17;6(2):e17118. doi: 10.1371/journal.pone.0017118.
• [18] CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis.Nat Cell Biol. 2018 Dec;20(12):1370-1377. doi: 10.1038/s41556-018-0228-7. Epub 2018 Nov 5.
• [19] Advances in the genetics of progressive myoclonus epilepsy.Am J Med Genet. 2001 Summer;106(2):129-38. doi: 10.1002/ajmg.1575.
• [20] Ocular morphology and function in juvenile neuronal ceroid lipofuscinosis (CLN3) in the first decade of life.Ophthalmic Genet. 2017 May-Jun;38(3):252-259. doi: 10.1080/13816810.2016.1210651. Epub 2016 Aug 2.
• [21] Btn2, a Hook1 ortholog and potential Batten disease-related protein, mediates late endosome-Golgi protein sorting in yeast.Mol Cell Biol. 2007 Jan;27(2):605-21. doi: 10.1128/MCB.00699-06. Epub 2006 Nov 13.
• [22] Neuronal vulnerability of CLN3 deletion to calcium-induced cytotoxicity is mediated by calsenilin.Hum Mol Genet. 2007 Feb 1;16(3):317-26. doi: 10.1093/hmg/ddl466. Epub 2006 Dec 22.
• [23] Discovery of a CLN7 model of Batten disease in non-human primates.Neurobiol Dis. 2018 Nov;119:65-78. doi: 10.1016/j.nbd.2018.07.013. Epub 2018 Jul 23.
• [24] Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease.Mol Ther. 2019 Oct 2;27(10):1836-1847. doi: 10.1016/j.ymthe.2019.06.015. Epub 2019 Jul 10.