It’s time for Batten disease research updates! BDSRA Foundation’s Head of Research & Medical Affairs, Dr. Ineka Whiteman, breaks down Batten disease clinical program updates, research news, and resources in her quarterly column, as seen in BDSRA’s monthly newsletter, The Illuminator.
With thanks to BDSRA Australia’s Tahmina Tabassum, PhD, for editorial assistance.
CLINICAL PROGRAM UPDATES
Clinical studies tracker
Keep up to date with the latest clinical trial and natural history study news with our Clinical Studies Chart on the BDSRA Foundation website. Check it out here.
THX Pharma and Biocodex announce a strategic licensing agreement – new hope for CLN3 Therapy
On February 11, THX Pharma (Theranexus), a biopharmaceutical company specializing in the treatment of rare neurological diseases, and Biocodex, an independent international pharmaceutical group, announced the execution of a strategic licensing agreement to advance the development of Batten-1 drug candidate for CLN3 therapy.
Batten-1 is currently preparing for a Phase 3 clinical trial, with initiation planned for 2026, and aims to become the first available therapy for CLN3. This license reflects a long-term ambition, with an international launch targeted around 2030. As part of the collaboration, THX Pharma will lead the Phase 3 study of Batten-1, with scientific and financial support from Biocodex.
Read the press release here.
On February 27, Beyond Batten Disease Foundation hosted a Family Research Update meeting providing key updates on the Batten-1/miglustat clinical program and timelines, and additional research developments in the CLN3 disease landscape.
Progress toward a gene therapy for CLN7 disease
Elpida Therapeutics recently published a historic milestone in the treatment of CLN7 Batten disease, with its Phase 1 study successfully testing the highest intrathecal dose of AAV9 gene therapy recorded, proving that high dose is safe and well-tolerated when paired with a rigorous immune-management protocol. While CLN7 disease typically involves a rapid and devastating decline, participants in this study showed signs of stabilization over a two-year period, maintaining respiratory function, avoiding G-tube surgeries, and achieving better seizure control. These findings provide vital safety information for the field, demonstrating that bypassing traditional dosing ceilings is possible and paving the way for a pivotal phase trial aimed at intervening earlier in the disease course.
Read the Phase 1 study results here.
Following this publication, Elpida hosted a community update for CLN7 families to hear directly from the Elpida team about their work to bring new treatment options to patients and families. During the session, Elpida shared the latest on the next steps for their new gene therapy program, including timelines for a natural history study, the Phase 2 trial, and how patients are being selected for participation.
Contact Eplida Therapeutics for further information on next steps: info@elpidatx.com.
FDA Unveils Plausible Mechanism Pathway for Bespoke Gene Therapies
The FDA just opened a major door for “bespoke” medicine— personalised treatments for a single person’s unique genetic code. In a ground-breaking move, the agency unveiled a new approval pathway called the “plausible mechanism framework” designed to reduce the timeline to get life-saving gene and RNA therapies to patients with ultra-rare diseases.
Historically, drug approval required large clinical trials with hundreds of people, an impossible requirement to meet for ultra-rare diseases. Under this new plan, if scientists can prove the exact disease mechanism and show that their custom CRISPR or RNA tool accurately fixes the known cause, the FDA can approve the treatment based on data from just a few patients. The agency will prioritize strong evidence of target engagement and well-characterized natural history data as external controls, potentially allowing data from just a few patients to support broader applications.
By accepting established biomarkers and focusing on stabilized disease progression rather than massive trial cohorts, the FDA is moving toward a future where personalised cures for ultra-rare conditions are a standard, accessible reality. Read the update here and find the FDA guidance document here.
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PUBLICATION HIGHLIGHTS: December 2025-February 2026
In this edition, we are delighted to showcase three publications co-authored by the BDSRA Foundation in the last quarter.
Articles are linked in each heading.
A timeline of symptom onset and disease progression in CLN3 disease.
Whiteman IT, Cook AL, Augustine EF, Bindoff AD, Johnson AM, Mason HL, Mink JW, Østergaard JR, Schulz A, Vermilion J, Vierhile A, Adams HR
Orphanet J Rare Dis. 2026 Jan 7. doi: 10.1186/s13023-025-04174-5. Online ahead of print. PMID: 41501856 No abstract available.
Summary: CLN3 disease is one of the most prevalent forms of Batten disease, usually beginning in the first decade of life and progressing in severity, with life expectancy in the 20’s or 30’s. Despite two decades of natural history studies, there has been no clearly defined timeline describing when key symptoms appear and how the disease progresses, making it difficult to plan optimal care and design effective clinical trials. Inspired by conversations with families and clinicians, and led by BDSRA’s Dr Ineka Whiteman together with investigators from the original natural history studies, this comprehensive meta-analysis brings together data from over 400 affected individuals to map the onset and progression of 13 core symptoms of classical CLN3 disease. The findings reveal a clear chronological pattern, beginning with early vision loss and advancing through cognitive, behavioural and motor decline, cardiac manifestations, feeding difficulties and end of life. By defining a clearer disease trajectory, this study offers practical anticipatory guidance for clinicians and families. It also highlights the need for standardised longitudinal natural history data to improve care and support future therapeutic development for CLN3 disease.
Limited enteric nervous system degeneration in human and murine CLN3 disease, is ameliorated by gene therapy in mice.
Ziółkowska EA, Williams LL, Jansen MJ, Wang SH, Eultgen EM, Sharma J, Sardiello M, Bradley RP, Whiteman IT, Sands MS, Heuckeroth RO, Cooper JD.
Acta Neuropathol Commun. 2025 Dec 22. doi: 10.1186/s40478-025-02205-7. Online ahead of print. PMID: 41430350 No abstract available.
Summary: Individuals with CLN3 disease frequently experience severe gastrointestinal (GI) problems that can significantly reduce quality of life and may contribute to death. This study shows a substantial loss of neurons and glia in the enteric nervous system – the master regulator of the bowel function – leading to bowel distension and impaired gut function. Importantly, AAV-mediated CLN3 gene therapy delivered systemically in CLN3-deficient mice prevented much of this nerve damage and preserved bowel function later in disease. This preclinical study provides early evidence that gene therapy may help address GI complications by targeting the underlying cause, expanding the field beyond our traditional understanding of Batten disease as a disorder of the central nervous system (CNS) only. This study also highlights the profound impact of patient organ donation. Examining bowel samples from individuals affected by Batten disease enables researchers to confirm that the disease effects observed in animal models is present, and therefore clinically relevant, in human patients. The generosity of families who choose to donate tissue makes it possible to study the disease directly, validate animal models, and move the field forward in meaningful ways.
Limited therapeutic efficacy of N-acetyl-L-leucine in a mouse model of CLN1 disease.
Ziółkowska EA, Pagán Torres NA, Chen H, Williams LL, Eultgen EM, Nowacka A, Dearborn JT, Nelvagal HR, Whiteman IT, Platt FM, Cooper JD.
Sci Rep. 2025 Dec 29. doi: 10.1038/s41598-025-32984-x. Online ahead of print. PMID: 41466111 No abstract available.
Summary: N-acetyl-L-leucine (NALL) is an oral compound with reported neuroprotective, anti-inflammatory and metabolic effects, recently approved for treatment of the lysosomal storage disorder Niemann-Pick disease type C. Researchers at The Washington University tested this agent in a mouse model of CLN1 disease to see whether NALL as a monotherapy (single therapy) could alleviate symptoms. Treatment was started either before symptoms appeared or after symptoms had begun and continued through advanced disease stages. The results showed that NALL alone did not meaningfully slow disease progression, improve overall motor function, reduce brain inflammation, or extend survival in this model, although a a modest, quantifiable benefit was observed on locomotor (walking) stability when treatment began early. These findings, although overall non-significant, provide important information in understanding the underlying biology of CLN1 disease. Moreover, as the authors state, “these negative results should not be interpreted as a dismissal of NALL’s therapeutic potential in general but rather as a demonstration of its limited value as a monotherapy in CLN1 disease.” Future research may be well directed toward testing NALL in combination therapy, in other NCL subtypes, or both.
Gastrointestinal symptoms in neuronal ceroid lipofuscinoses (NCLs): an observational study on prevalence, timing of progression, and impact on quality of life.
Della Vecchia S, Simonati A, Manca ML, Pietrafusa N, Trivisano M, Calabrese C, Specchio N, Santorelli FM; A-NCL-ETS.
Neurogenetics. 2025 Dec 11;26(1):88. doi: 10.1007/s10048-025-00871-2. PMID: 41379326
Summary: Severe gastrointestinal (GI) symptoms are commonly reported in children and young people with Batten disease and represent a significant yet under-recognised contributor to disease burden. For the first time in humans, a cross-sectional study in an Italian NCL cohort has systematically assessed the burden of GI manifestations using a standardized assessment tool combined with structured caregiver interviews. More than 60% of individuals experienced GI issues, with constipation frequently appearing early and dysphagia emerging later, both having a profound impact on quality of life. Notably, swallowing and feeding problems correlated with neurological disease severity, whereas constipation did not, suggesting distinct underlying mechanisms. These findings highlight the need for routine, proactive GI screening in individuals with Batten disease and recognises the importance of considering GI outcomes in the design and evaluation of future therapeutic trials.
CLN3 mediates chloride efflux from lysosomes.
Wang Y, Li K, Chen W, Chen C, Yong AJH, Zhang X, Tynan-La Fontaine M, Jan YN, Jan LY.
Neuron. 2026 Jan 19:S0896-6273(25)00886-4. doi: 10.1016/j.neuron.2025.11.013. Online ahead of print. PMID: 41558486
First Reported Case of CLN5 Disease in Japan: Identification of a Novel Homozygous Pathogenic Variant Through Whole Genome Sequencing.
Nishi E, Yanagi K, Shima M, Yamazaki N, Kawato K, Narita A, Sakai N, Okamoto N, Yanagihara K, Kaname T.
Clin Case Rep. 2025 Dec 30;14(1):e71739. doi: 10.1002/ccr3.71739. eCollection 2026 Jan. PMID: 41479428 Free PMC article.
Brain-Directed AAV Gene Therapy Rescues a Mouse Model of the CLN5 Form of Neuronal Ceroid Lipofuscinosis Disease and Normalizes a Blood Plasma Biomarker of Neurodegeneration.
Liu W, Geard AF, Massaro G, Hughes MP, Aristorena M, Coombe-Tennant O, Xu L, Semenyuk O, Bush R, Te Vruchte D, Priestman D, Laban R, Veleva E, Heslegrave AJ, Zetterberg H, Platt FM, Smith AJ, Mole SE, Ali RR, Rahim AA.
Hum Gene Ther. 2025 Dec 16. doi: 10.1177/10430342251403448. Online ahead of print. PMID: 41457644
Incidence and timing of diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2): A nationwide study using the French hospital discharge database.
Auvin S, Hamandjian MA, Karam P, Hoebeke C.
Eur J Paediatr Neurol. 2025 Dec 3;60:44-49. doi: 10.1016/j.ejpn.2025.12.001. Online ahead of print. PMID: 41354011
Persistent lymphopenia in a Japanese boy with neuronal ceroid lipofuscinosis type 3.
Kajiwara K, Liang Q, Uchiyama Y, Chong PF, Ichimiya Y, Monji N, Shimokawa S, Sonoda M, Watanabe E, Sakata A, Sonoda Y, Akamine S, Ishimura M, Murakami Y, Kunisaki Y, Sonoda KH, Matsumoto N, Sakai Y, Ohga S.
Eur J Med Genet. 2025 Dec;78:105058. doi: 10.1016/j.ejmg.2025.105058. Epub 2025 Nov 5. PMID: 41203069
Longitudinal Exploration of Auditory Sensory-Perceptual Processing in CLN3 Disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): A High-Density Auditory Evoked Potential (AEP) Study.
Bojanek EK, Lang ER, Adams HR, Vermilion J, Augustine EF, Brima T, Nasimjonova S, Freedman EG, Foxe JJ.
bioRxiv [Preprint]. 2025 Nov 20:2025.11.19.689311. doi: 10.1101/2025.11.19.689311. PMID: 41332681. Free PMC article. Preprint.
Enzyme replacement therapy for CLN1 batten disease that crosses the blood-brain-barrier.
Raman R, Horst B, Shahrokh Z, Hatambeygi N, Zare M, Leszczyniecka M, Harris JS, Banks WA, Hansen KM, Erickson MA, Ekins S.
Mol Genet Metab. 2026 Jan 16;147(3):109733. doi: 10.1016/j.ymgme.2026.109733. Online ahead of print. PMID: 41576655
Neurodevelopmental and Psychiatric Disorders and the Use of Psychotropic Medications in a National Sample of Individuals With Juvenile Neuronal Ceroid Lipofuscinosis.
Oerbeck B, Helland IB, Adams HR, Overgaard KR.
J Child Neurol. 2026 Feb 5:8830738251413827. doi: 10.1177/08830738251413827. Online ahead of print. PMID: 41642869
Dysfunction of GABAergic interneurons underlies altered neural network oscillations associated with epileptiform activity in PPT1-deficient mice.
Tong J, Liu W, Wang Q, Yang H, Gao Z, Wu W, Liu J, Li W, Lu C.
Transl Psychiatry. 2026 Feb 2;16(1):106. doi: 10.1038/s41398-026-03843-8. PMID: 41629288
Investigating the impact of music for children with Batten disease
Rebecca Atkinson
British Journal of Music Therapy doi: 10.1177/13594575261423388. First published online February 15, 2026
RESEARCH UPDATES
Preclinical study on oral N-acetyl-L-leucine (NALL) as a monotherapy shows limited effectiveness for CLN1 disease.
N-acetyl-L-leucine (NALL) is an oral compound with reported neuroprotective, anti-inflammatory, and metabolic effects, recently approved for the treatment of the lysosomal storage disorder Niemann-Pick disease type C. This agent was tested in a mouse model of CLN1 disease to see whether NALL, as a monotherapy (single therapy), could alleviate symptoms. Treatment was initiated either before symptoms appeared or after they began, and continued through advanced disease stages. The results showed that NALL alone did not meaningfully slow disease progression, improve overall motor function, reduce brain inflammation, or extend survival in this model. However, a modest, quantifiable benefit was observed on locomotor (walking) stability when treatment began early.
These findings, although overall non-significant, provide important information in understanding the underlying biology of CLN1 disease. Moreover, as the authors state, “These negative results should not be interpreted as a dismissal of NALL’s therapeutic potential in general but rather as a demonstration of its limited value as a monotherapy in CLN1 disease.”
Future research may be well directed toward testing NALL in combination therapy, in other NCL subtypes, or both. This study was co-authored by our Head of Medical Affairs and Research, Dr. Ineka Whiteman, and can be found here.
