Batten Disease Support and Research Association Australia

Articles are linked to in each heading.

Research priorities for the neuronal ceroid lipofuscinoses.

Augustine EF, Moore N, Abreu NJ, Berry-Kravis E, Do AND, Parker AF, James S, Siedman N, Vermilion J, Vierhile A, Wang RY, Whiteman IT; Batten Disease Clinical Research Consortium. Lancet Neurol. 2025 Oct;24(10):811-812. doi: 10.1016/S1474-4422(25)00317-5. PMID: 40975092 Summary: To help guide progress, the now NIH-funded Batten Disease Clinical Research Consortium (BDCRC), a US-based academic network, launched a priority-setting initiative in 2024 driven by stakeholders. Using a modified James Lind Priority Setting Partnership approach, nearly 200 global participants contributed 475 research questions, which were refined and ranked through a second survey. This process identified 12 top research priorities spanning disease mechanisms, earlier diagnosis, symptom management, broader life impacts, and development of effective therapies. These priorities are now shaping the first major BDCRC research project and guiding new global funding efforts, including six inaugural grants awarded in 2025 by the Batten Disease Global Research Initiative. Collectively, this work lays a coordinated roadmap to accelerate meaningful advances for the Batten disease community.

Visual Recovery and Neurological Stabilization Following Miglustat Treatment in Pediatric CLN3 Disease.

Dutton AE, Whiteman IT, Jones MM, Geering KE, Afshar S, Johnson AM, Grigg JR. J Child Neurol. 2025 Sep 18:8830738251374538. doi: 10.1177/08830738251374538. Online ahead of print. PMID: 40966007 Summary: This prospective case report, co-authored by BDSRA Australia’s Dr Ineka Whiteman, Medical & Scientific Advisory Board Members Prof. John Grigg and Dr Alex Johnson, along with colleagues from Sydney Children’s Hospital Network, followed two sisters with genetically confirmed CLN3 disease who received oral, weight-based miglustat for 18 months under off-label use. Both children showed encouraging early signs of benefit, including improved visual acuity and clinical stabilization, with one also demonstrating gains in adaptive functioning. Treatment was well-tolerated with no significant adverse effects. While these preliminary findings suggest that miglustat may offer short-term clinical benefit, especially when started earlier in the disease course, long-term studies on a larger cohort are needed to fully assess its safety and effectiveness for CLN3 disease.

Prime editing-installed suppressor tRNAs for disease-agnostic genome editing.

Pierce SE, Erwood S, Oye K, An M, Krasnow N, Zhang E, Raguram A, Seelig D, Osborn MJ, Liu DR. Nature. 2025 Nov 19. doi: 10.1038/s41586-025-09732-2. PMID: 41261131 Summary: David Liu’s Lab from Broad Institute of Harvard and MIT has recently reported new prime editing strategy to overcome disease-causing premature stop codons. In CLN2 models. editing efficiencies were high and 17–70% of normal TPP1 enzyme activity was restored. This treatment also restored full-length TPP1 protein to levels that meet the known therapeutic threshold for CLN2. The findings highlight its strong potential as a therapeutic approach for Batten Disease.

The missing piece: Solving the 50-year puzzle of BMP synthesis in neurodegeneration.

Uche Medoh Science. 2025 Nov 13;390(6774):685-686. doi: 10.1126/science.aec9580. Epub 2025 Nov 13. PMID: 41231989. Summary: Dr. Uche Moedoh from the Abu-Remaileh Lab at Stanford University serendipitously identified the long-sought enzyme that produces bis(monoacylglycero)phosphate (BMP), a key lipid that enables lysosomes to break down fats. While investigating the gene CLN5, he found that its loss nearly eliminates BMP and causes a dramatic build-up of its precursor revealing that CLN5 is responsible for BMP production. This breakthrough exhibits lysosomes can synthesize complex lipids and links disrupted BMP production to toxic lipid accumulation across neurodegenerative diseases, opening new therapeutic possibilities aimed at restoring healthy lipid balance in the brain.

Canine Neuronal Ceroid Lipofuscinosis-like Disorder Associated with Sequence Variants in AP3B1 and TRAPPC9.

Then A, Welly R, Bullock G, Chevallier L, Katz ML. Genes (Basel). 2025 Nov 11;16(11):1370. doi: 10.3390/genes16111370. PMID: 41300827

Lysosomal TRPML1 activation modulates synaptic transmission and intrinsic neuronal excitability.

Wani MA, Hall CM, Mittmann T, Engelhardt JV, Grünewald B. Neuropharmacology. 2025 Nov 10:110764. doi: 10.1016/j.neuropharm.2025.110764. Online ahead of print. PMID: 41223937

Sex-specific and age-related progression of auditory neurophysiological deficits in the Cln3 mouse model of Batten disease.

Ding Y, Feng J, Prifti V, Rico GA, Solorzano AG, Chang HE, Freedman EG, Foxe JJ, Wang KH. J Neurodev Disord. 2025 Nov 6;17(1):67. doi: 10.1186/s11689-025-09652-2. PMID: 41199165 Free PMC article.

Loss of the lysosomal protein CLN3 triggers c-Abl-dependent YAP1 pro-apoptotic signaling.

Domingues N, Calcagni' A, Freire S, Pires J, Casqueiro R, Salazar IL, Herz NJ, Huynh T, Wieciorek K, Outeiro TF, Girão H, Milosevic I, Ballabio A, Raimundo N. EMBO Rep. 2025 Nov 6. doi: 10.1038/s44319-025-00613-3. Online ahead of print. PMID: 41198904

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. Nucleic Acids Res. 2025 Oct 28;53(20):gkaf1141. doi: 10.1093/nar/gkaf1141. PMID: 41189054 Free PMC article.

CLN7 protein functions at the interface between endolysosomes and stress granules to promote cell survival.

Sharaireh A, Guevara-Ferrer M, Ludlaim AM, Humphries JD, Phillips AM, Dowsey AW, Zhang Z, Counsell JR, Unwin RD, Mole SE, Rahim AA, McKay TR. Cell Death Dis. 2025 Oct 31;16(1):772. doi: 10.1038/s41419-025-08063-4. PMID: 41173878 Free PMC article.

Chest-sited intraventricular access devices for cerliponase alfa infusion in Batten disease at a single tertiary United Kingdom pediatric center.

Read J, Donald A, Rhead S, Acquaah L, Chan G, Heap F, Brown B, Ghosh A, Jones SA, Ram D, Kamaly-Asl I. J Neurosurg Pediatr. 2025 Oct 31:1-8. doi: 10.3171/2025.7.PEDS25222. Online ahead of print. PMID: 41172362

Treatment of Neuronal Ceroid Lipofuscinosis Type 2 with Cerliponase Alfa: A Systematic Review and Single-Arm Meta-Analysis of Two Studies.

Oliveira JA, Saddique MN, Qadri M, Shahid F, de Jesus ACFS, Sarmento FP. J Child Neurol. 2025 Oct 29:8830738251389180. doi: 10.1177/08830738251389180. Online ahead of print. PMID: 41160491 Review.

Long-Term Open-Label Study Evaluating Oral Miglustat Treatment in Patients With Neuronal Ceroid Lipofuscinosis Type 3.

Pietrafusa N, Trivisano M, Calabrese C, De Dominicis A, Cappelletti S, Correale C, Salimbene L, Vallesi L, Corsetti T, Specchio N. Neurology. 2025 Oct 7;105(7):e214110. doi: 10.1212/WNL.0000000000214110. Epub 2025 Sep 9. PMID: 40924969 Free PMC article. Clinical Trial.

Is Miglustat an Effective Treatment for CLN3 (Batten) Disease?

Mink JW, Vermilion J. Neurology. 2025 Oct 7;105(7):e214224. doi: 10.1212/WNL.0000000000214224. Epub 2025 Sep 9. PMID: 40924968 No abstract available.

Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.

Zió?kowska EA, Takahashi K, Dickson PI, Sardiello M, Sands MS, Cooper JD. Nat Rev Neurol. 2025 Nov;21(11):606-622. doi: 10.1038/s41582-025-01132-4. Epub 2025 Sep 4. PMID: 40908342 Review.

Caudate serotonin signaling during social exchange distinguishes essential tremor and Parkinson's disease patients.

Hartle AE, Kishida KT, Sands LP, Batten SR, Barbosa LS, Bang D, Lohrenz T, White JP, K Sohrabi A, Calafiore RL, DiFeliceantonio AG, Laxton AW, Tatter SB, Witcher MR, Montague PR, Howe WM. Nat Commun. 2025 Sep 2;16(1):7958. doi: 10.1038/s41467-025-63079-w. PMID: 40897696 Free PMC article.

Discovery of Functionalized 1H-Benzo[d]imidazoles That Confer Protective Effects in a Phenotypic CLN3 Disease Patient-Derived iPSC Model.

Simeon P, Venkatesan R, Hao X, Carmona AV, Daria S, Alnouti Y, Trippier PC. J Med Chem. 2025 Sep 11;68(17):18530-18552. doi: 10.1021/acs.jmedchem.5c01369. Epub 2025 Sep 1. PMID: 40888168

Correction: Open-label evaluation of oral trehalose in patients with neuronal ceroid lipofuscinoses.

Della Vecchia S, Gammaldi N, Ricca I, Mero S, Doccini S, Ardissone A, Bagnoli S, Battini R, Colombi E, Favaro J, Furlan R, Giordano L, Ingannato A, Mandelli A, Manzoni FMP, Milito G, Moroni I, Nacmias B, Nardocci N, Parmeggiani L, Pezzini F, Pietrafusa N, Sartori S, Specchio N, Trivisano M, Ets ACL, Simonati A, Santorelli FM; A-NCL ETS Group. J Neurol. 2025 Oct 15;272(10):696. doi: 10.1007/s00415-025-13358-9. PMID: 41091215 No abstract available.

Buried Bumper Syndrome With Full Gastric Wall Penetration Managed With Delayed Replacement: A Conservative Approach.

Nguyen HTK, Pfeiffer B, Evanoff T, Yatsu J, Hor MK. Cureus. 2025 Sep 12;17(9):e92137. doi: 10.7759/cureus.92137. eCollection 2025 Sep. PMID: 41084679 Free PMC article.

Bioenergetic Profiling Applied to a Zebrafish Model of Neuronal Ceroid Lipofuscinosis, a Lysosomal Storage Disorder.

Marchica V, Young EM, Ramdeen N, Simbi B, Russell C. Methods Mol Biol. 2026;2976:209-225. doi: 10.1007/978-1-0716-4844-5_15. PMID: 41082122

Determining Lysosomal Enzyme Activity Using Fluorogenic Probes.

Sauvageau E, Lefrancois S. Methods Mol Biol. 2026;2976:1-10. doi: 10.1007/978-1-0716-4844-5_1. PMID: 41082108

Elevated tripeptidyl-peptidase 1 corrects multiple disease phenotypes in a mouse model of juvenile neuronal ceroid lipofuscinosis.

Banach-Petrosky W, Larrimore KE, Sleat EH, Bazer A, Samuels B, Tan Y, Melton AC, Ichida JK, Logan TP, Lobel P, Sleat DE. Mol Ther Methods Clin Dev. 2025 Sep 3;33(4):101587. doi: 10.1016/j.omtm.2025.101587. eCollection 2025 Dec 11. PMID: 41049692 Free PMC article.

Atlas of Lysosomal Aging Reveals a Molecular Clock of Storage Disorder-Associated Metabolites.

Puszynska AM, Nguyen TP, Cangelosi AL, Armani A, Roberts JM, Singh KA, Cameron JC, Tseyang T, Liu GY, Lai S, Sprenger HG, Yang J, Colgan WN, Kedir JF, Kajderowicz KM, Esantsi TK, Lu YR, Waite M, Kunchok T, Lewis CA, Schulte F, Bell GW, Sabatini DM, Weissman JS. bioRxiv [Preprint]. 2025 Sep 26:2025.09.25.678303. doi: 10.1101/2025.09.25.678303. PMID: 41040360 Free PMC article. Preprint.

The first report of ceroid lipofuscinosis type 11 in China: a novel mutation of GRN and updated clinical review.

Shi D, Bao J, Wu H, Huang B, Zheng Y, Xu F, Wang H, Liu J, Guan S, Du K. Neurol Sci. 2025 Nov;46(11):5741-5749. doi: 10.1007/s10072-025-08472-5. Epub 2025 Sep 29. PMID: 41021155 Review.

Palmitoyl-Protein Thioesterase 1 (PPT1) Protein, Linked to Neuronal Ceroid Lipofuscinosis 1, Is a Major Constituent of Ageing-Related Human Neuronal Lipofuscin.

Anstötz M, Tschirner S, May C, Kösters S, Martin C, Caspers S, Aronica E, Bidmon HJ, Marcus K, Korth C. Neuropathol Appl Neurobiol. 2025 Oct;51(5):e70043. doi: 10.1111/nan.70043. PMID: 40990621 Free PMC article.

Assessment of motor deterioration in a cynomolgus macaque with neuronal ceroid lipofuscinosis type 2 disease using two behavioral analyses.

Munesue Y, Ono F, Ageyama N, Yagami KI, Ishii K, Tamaoka A, Yasutomi Y, Shimozawa N. J Vet Med Sci. 2025 Nov 1;87(11):1221-1226. doi: 10.1292/jvms.25-0314. Epub 2025 Sep 18. PMID: 40967783 Free PMC article.

PUBLICATION HIGHLIGHTS – September to November 2025