Articles are linked to in each heading.

Neuronal Ceroid Lipofuscinoses Overview

Malik K, Santucci K, Sremba L, Steenari M, Miele A, Demarest S and Whiteman I. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Summary: This article, co-authored by Dr Ineka Whiteman and colleagues from Children’s Hospital Colorado and Children’s Hospital Orange Country, provides an updated overview of clinical characteristics and genetic causes of all Batten disease (NCL) subtypes. It also discusses clinical evaluation strategies to identify the genetic cause of NCLs, review of management, and approaches to informed counselling of family members of affected individuals.

Same-Day Approach for Combined Intravitreal and Intracerebroventricular Enzyme Replacement Therapy to Prevent Retinal Disease Progression in Children With Neuronal Ceroid Lipofuscinosis Type 2.

Rogers DL, Blind JE, Kienzle T, De Los Reyes E, Mendel TA, Jordan CO. Pediatr Neurol. 2025 Jun 10;170:1-3. doi: 10.1016/j.pediatrneurol.2025.06.007. Online ahead of print. Summary: The Nationwide Children’s Hospital Batten Center (Columbus, Ohio USA) have developed new clinical pathway for same-day administration of both intravitreal (eye) and intracerebroventricular (brain) cerliponase alfa to treat individuals with CLN2 disease, using a preparation technique that takes advantage of the overfill in the vial. This approach aims to slow not only motor decline but also vision loss, offering a more comprehensive treatment option.

Impact of CLN3 Disease on Child Quality of Life and Family Function.

Vermilion J, Augustine EF, Mink JW, McDermott MP, Vierhile A, Pereira-Freitas M, Adams HR. Pediatr Neurol. 2025 Jun 16;170:17-25. doi: 10.1016/j.pediatrneurol.2025.06.008. Online ahead of print. Summary: A new study from the University of Rochester Batten Center (NY, USA) shows that children with CLN3 disease have significantly reduced quality of life, which worsens as the disease progresses. While families report a substantial overall impact, this does not appear to change in line with symptom severity, highlighting the ongoing need for targeted support for both patients and caregivers.

The Wechsler intelligence scale for children, fourth and fifth editions perform comparably in children with Batten disease.

Adams HR, Augustine EF, Bonifacio K, Collins A, Vierhile AE, Mink JW. Orphanet J Rare Dis. 2025 Aug 7;20(1):413. doi: 10.1186/s13023-025-03923-w. Summary: Researchers at the University of Rochester Batten Center (NY, USA) found that two versions of a common cognitive test, the WISC-IV and WISC-V, produce comparable results in children and young adults with Batten disease. This means data from both versions can be combined to better understand the cognitive decline associated with the disease over time.

Recreating pathophysiology of CLN2 disease and demonstrating reversion by TPP1 gene therapy in hiPSC-derived retinal organoids and retina-on-chip.

Corti S, Kim KH, Chen T, Botezatu A, Cora V, Ma K, Pashkovskaia N, Bernal Vergara A, Sperlich D, Dave K, Tolone A, Reddinger RM, Tully CB, Higgins M, Kleger A, Breunig M, Lopatta P, Wingerter S, Cipriano M, Bolz S, Ueffing M, Buss N, Loskill P, Liebau S, Achberger K. Cell Rep Med. 2025 Aug 19;6(8):102244. doi: 10.1016/j.xcrm.2025.102244. Epub 2025 Jul 23.

Cerliponase alfa therapy leads to long-term seizure freedom in a patient with late infantile neuronal ceroid lipofuscinosis

Anita N Datta, Sylvia Stockler PMID: 40865184 DOI: 10.1016/j.seizure.2025.08.024

Natural history and variants in neuronal ceroid lipofuscinoses: Uncoupling genotype and phenotype.

Mole SE. Dev Med Child Neurol. 2025 Aug 2. doi: 10.1111/dmcn.16442. Online ahead of print.

Milasen: The Emerging Era of Patient-Customized N-of-1 Antisense Oligonucleotides as Therapeutic Agents for Genetic Diseases.

Wilton-Clark H, Yan E, Yokota T. Methods Mol Biol. 2025;2964:85-93. doi: 10.1007/978-1-0716-4730-1_4.

Age at onset and gene variants predict lifespan and disease duration in childhood neuronal ceroid lipofuscinoses.

Simonati A, Pezzini F, Nardocci N; CLNet Consortium; Santorelli FM. Dev Med Child Neurol. 2025 Jul 24. doi: 10.1111/dmcn.16416. Online ahead of print.

Gene therapy ameliorates neuromuscular pathology in CLN3 disease.

Zió?kowska EA, Jablonka-Shariff A, Williams LL, Jansen MJ, Wang SH, Eultgen EM, Wood MD, Hunter DA, Sharma J, Sardiello M, Reese R, Pestronk A, Sands MS, Snyder-Warwick AK, Cooper JD. Acta Neuropathol Commun. 2025 Jul 23;13(1):160. doi: 10.1186/s40478-025-02059-z.

Autosomal dominant Kufs disease in a Georgian adult woman: A case report.

Papiashvili N, Gagua S, Gonjilashvili N, Okujava N, Tsereteli A. Epilepsy Behav Rep. 2025 Jul 10;32:100805. doi: 10.1016/j.ebr.2025.100805. eCollection 2025 Dec.

Case Report: The window that closed too soon: lessons from a late CLN2 diagnosis and death of a 9-year-old boy.

Bryzik A, Larysz D, Larysz P, Karpierz JI, Paprocka J. Front Genet. 2025 Jul 4;16:1622185. doi: 10.3389/fgene.2025.1622185. eCollection 2025.

AAV-delivered PPT1 provides long-term neurological benefits in CLN1 mice and achieves therapeutic levels in sheep brain.

Alam MS, Khatiwada A, Eaton SL, Cohen DM, White J, Derby M, Peterson D, Rivera-Pena G, Nayal M, Becker M, Beck H, Li C, Gentzel R, Atkins G, Greenhalgh SN, Lillico SG, Gregson R, Clutton E, Murdoch F, Nixon J, Gray M, Thompson G, McBride J, Wishart TM, Biferi MG, Ramsburg E. Mol Ther. 2025 Jul 17:S1525-0016(25)00546-5. doi: 10.1016/j.ymthe.2025.07.011. Online ahead of print.

Downregulation of AKT-mediated p27Kip1 phosphorylation with shift to sphingomyelin synthesis in CLN3 disease.

Bilal F, Soueid J, Saab S, Makhoul N, Hamze Z, El-Bazzal L, Makoukji J, Boustany RM. IBRO Neurosci Rep. 2025 Jun 27;19:223-234. doi: 10.1016/j.ibneur.2025.06.005. eCollection 2025 Dec.

Glucosylsphingosine is a potential fluid-based biomarker of lysosomal dysfunction in Cln3?ex7/8 mice.

Wald H, Cicalese S, Yao L, Hatcher N, Luo W, Shen X, Ping X, Culp B, Metzger D, Ault M, Nunes C, Cosden M, Jinn S, Uslaner J, Smith S, Marcus J, Drolet R. Neurobiol Dis. 2025 Jul 8;214:107026. doi: 10.1016/j.nbd.2025.107026. Online ahead of print.

CLN3 disease disrupts very early postnatal hippocampal maturation.

Singh JB, Burris DM, Bhuyan S, Thurston T, Oschmann A, Jankowski C, Lu W, Rabinowitz JD, Ahrens-Nicklas RC. Sci Rep. 2025 Jul 8;15(1):24411. doi: 10.1038/s41598-025-02010-1.

Unraveling Neuronal Ceroid Lipofuscinosis: Insights From Two Pediatric Cases in Peripheral India.

Aman N, Panapil AG, Utage P. J Child Neurol. 2025 Jun 22:8830738251346920. doi: 10.1177/08830738251346920. Online ahead of print.

Benchmarking Nanopore Sequencing for CLN2 (TPP1) Mutation Detection: Integrating Rapid Genomics and Orthogonal Validation for Precision Diagnostics.

Teker B, Akan G, Kazan HH, Özgen Ö, Tatonyan S, Balci MC, Karaca M, Kurekci F, Y?ld?z EP, Güngor O, Deniz A, Gedikbasi A, Atalar F, Gokcay GF, Poda M. Int J Mol Sci. 2025 May 23;26(11):5037. doi: 10.3390/ijms26115037.

Mistargeting and ER retention of CLN7 patient-associated nonsense and sequence deletion mutations as a novel cause for CLN7 disease.

Valigi F, Uebler L, Storch S. Hum Mol Genet. 2025 Jun 9:ddaf089. doi: 10.1093/hmg/ddaf089. Online ahead of print.

Therapeutic antisense oligonucleotide mitigates retinal dysfunction in a pig model of CLN3 Batten disease.

Stratton MP, Centa JL, Swier VJ, Pfeifer WL, Booth CD, Albert K, Hunyara JL, Rechtzigel MJ, Duelli FJ, Leppert HG, Rigo F, Smit T, Jafar-Nejad P, Weimer JM, Drack AV, Hastings ML. bioRxiv [Note: this is a Preprint, not yet peer-review published]. 2025 May 31:2025.05.30.656864. doi: 10.1101/2025.05.30.656864.

Neuronal lipofuscinosis caused by Kufs disease/CLN4 DNAJC5 mutations but not by a CSP?/DNAJC5 deficiency.

López-Begines S, Borjini N, Lavado-Roldán Á, Mesa-Cruz C, Mavillard F, Wiersma VI, Rubio-Pastor F, Tumini E, Paradela-Leal C, Chiclana-Valcárcel ML, Aguado C, Luján R, Scheper W, Nieto-González JL, Fernández-Chacón R. Sci Adv. 2025 May 23;11(21):eads3393. doi: 10.1126/sciadv.ads3393. Epub 2025 May 21.

UNRAVELING CLN7 disease: the distinct roles of two close MFSD8/CLN7 splice variants in phenotypic expression.

Venier AC, Savy S, Carro G, Guelbert G, Grondona E, Guelbert N, Nicola JP, Pesaola F, De Paul AL. Hum Mol Genet. 2025 Jun 18;34(13):1157-1167. doi: 10.1093/hmg/ddaf067.

Genetic Reasons for Phenotypic Diversity in Neuronal Ceroid Lipofuscinoses and High-Resolution Imaging as a Marker of Retinal Disease.

Huey J, Gupta P, Wendel B, Liu T, Bharadwaj P, Schwartz H, Kelly JP, Chang I, Chao JR, Sabesan R, Nagiel A, Mustafi D. Ophthalmol Sci. 2024 May 29;4(6):100560. doi: 10.1016/j.xops.2024.100560. eCollection 2024 Nov-Dec.

Defective anterograde protein-trafficking contributes to endoplasmic reticulum-stress in a CLN1 disease model.

Plavelil N, Appu AP, Gopal KC, Mondal A, Perkins N, Mukherjee AB. Neurobiol Dis. 2025 Jun 1;209:106890. doi: 10.1016/j.nbd.2025.106890. Epub 2025 Mar 28.

Characterisation of sleep in a mouse model of CLN3 disease revealed sex-specific sleep disturbances.

Kane KM, Iradukunda D, McLouth CJ, Guo LZ, Wang J, Subramoniam A, Huffman D, Donohue KD, O'Hara BF, Sunderam S, Wang QJ. J Sleep Res. 2025 Aug;34(4):e14461. doi: 10.1111/jsr.14461. Epub 2025 Jan 28.