Brineura (cerliponase alfa) / BioMarin - LARVOL DELTA

Clinical experience in three CLN2 patients: enzyme replacement effects and strategies after treatment discontinuation (SSIEM 2026) - "in our experience, ERT with cerliponase alfa was associated with stabilization of motor and language function and improved seizure control. Miglustat may be considered as a potential alternative strategy in exceptional clinical situations in which ERT cannot be continued."

Clinical • Cardiovascular • CNS Disorders • Epilepsy • Hypertension • Infectious Disease • TPP1

Neurodegeneration biomarkers in CLN2: CSF neurofilament light chain levels in patients treated with cerliponase alfa (SSIEM 2026) - "These findings support the utility of CSF NfL as a biomarker for neuroaxonal damage and treatment response in CLN2. The sustained reduction of NfL suggests a neuroprotective effect of cerliponase alfa. Importantly, this study indicates that NfL reduction is more pronounced in atypical and presymptomatic cases, suggesting that early intervention significantly mitigates axonal injury."

Biomarker • Clinical • CNS Disorders • Epilepsy • CSF NfL • NEFL • TPP1

Cerliponase alfa for the treatment of CLN2 disease: Combined results from two ongoing observational studies (SSIEM 2026) - P | "Treatment with cerliponase alfa demonstrated safety and effectiveness outcomes in a real-world setting that were consistent with clinical trial findings."

Clinical • Observational data

Presymptomatic and symptomatic disease stage-associated outcomes of cerliponase alfa treatment in siblings with CLN2 disease (SSIEM 2026) - "These real-world, intrafamilial data quantify stage-associated benefits of ICV-ERT across functional and developmental outcomes and seizures. Our findings support the importance of newborn screening and early treatment initiation. Moreover, they will help physicians to provide families with transparent and realistic guidance regarding the expected therapeutic benefit and to design individualized treatment strategies tailored to each patient."

CNS Disorders • Epilepsy • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • TPP1

Mapping Clinical Progression to Brain Atrophy in CLN2 Patients Under Cerliponase Alfa Treatment: A Prospective Neuroimaging Study. (PubMed, J Inherit Metab Dis) - "Leveraging connectome data, we demonstrated that atrophy was linked to brain network architecture. Given their strong associations with clinical outcomes, MRI-based brain morphometric measures are promising CLN2 disease biomarkers to aid diagnosis, monitor disease progression, and guide therapy."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Epilepsy • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Rare Diseases

A 3 and 6 month GLP toxicology study in cynomolgus monkeys of a single intracerebroventricular dose of LTS-101 to support development as an AAV gene therapy candidate for treatment of CLN2 Batten disease (ASGCT 2026) - "While bi-monthly infusions of recombinant human TPP1 (cerliponase alfa) to the brain have provided benefit to patients, significant disease burden remains and the therapy requires families to relocate in proximity to infusion centers for the frequent, hours long, infusions...All animals were immunosuppressed with prednisone and tacrolimus...Clinical development planning is progressing in collaboration with world-leaders in CLN2 disease. LTS-101 is a promising gene therapy candidate with the potential to treat CLN2 Batten disease patients with a one-time ICV administration providing stable, long-term expression of TPP1 while eliminating the caregiver and patient burden of repeated ERT treatments."

Gene therapy • CNS Disorders • Gene Therapies • Ophthalmology • TPP1

Update on the TTX-381 gene therapy clinical trial for CLN2 Batten disease-related retinopathy (ARVO 2026) - "A human recombinant form of this enzyme, cerliponase alfa, is approved to slow loss of developmental milestones in children with CLN2 disease, although intracerebroventricular delivery does not affect the ocular manifestations of the disease.TTX-381 is an investigational AAV9 gene therapy designed to deliver a human CLN2 transgene to induce sustained secretion of TPP1 enzyme to prevent progressive photoreceptor (PR) degeneration following a one-time subretinal administration...The treatment has remained safe, and treated eyes showed measurable TPP1 and clear signs of slowing or even partial reversal of retinal degeneration, unlike untreated eyes. These results informed the design of a larger pivotal study, for which early data are now emerging."

Clinical • Gene therapy • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • TPP1

Feasibility and Tolerability of Intravitreal Cerliponase Alfa in CLN2 Disease: A Pediatric Case Report (ARVO 2026) - "While these observations are early and limited to a single patient, they offer practical insight into how emerging vision-preserving strategies may fit into real-world CLN2 care. Longer-term follow-up and broader clinical experience will be essential to understand the true safety and potential impact of this approach for children with CLN2."

Case report • Clinical • Ophthalmology

Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2 (clinicaltrials.gov) - P1/2 | N=5 | Active, not recruiting | Sponsor: David L Rogers, MD | Trial completion date: Nov 2027 ➔ Mar 2027 | Trial primary completion date: Nov 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • CNS Disorders • Ophthalmology • Retinal Disorders

Patient and Family Perspective on Transition from Ventricular Access Device to Chest-Sited Port for Intracerebroventricular Infusion in CLN2 Disease. (PubMed, Children (Basel)) - "This caregiver-centered case report highlights how access device choice meaningfully shapes treatment burden, safety planning, and daily life for families managing CLN2 disease. As chest-port methodologies become adopted, incorporating caregiver and patient perspectives is essential to developing patient-centered treatment options for long-term intracerebroventricular therapy."

Journal • CNS Disorders • Pediatrics

CLN2 disease: why early diagnosis matters more than ever. (PubMed, Eur J Paediatr Neurol) - No abstract available

Journal • CNS Disorders • Epilepsy • Pediatrics • Rare Diseases

Natural-History Mapping of Lysosomal Storage Disorders (LSDs): Gaucher Disease as a Model for Precision Care. (PubMed, J Inherit Metab Dis) - P | "Key observations include: (i) Whole-gene sequencing has expanded genotype-phenotype maps, revealing more than 70 recombinant GBA alleles that confound panel tests; (ii) registry trajectories suggest that formal multi-state models could capture treatment-modified courses and silent endpoints-monoclonal gammopathy, malignancy, Parkinson's disease, pulmonary arterial hypertension-better than current summary statistics; (iii) lyso-Gb1 outperforms legacy biomarkers and now serves as a second-tier newborn-screening marker; (iv) Robust natural-history evidence has already underpinned regulatory approvals across several lysosomal disorders-including olipudase alfa for ASMD, cerliponase alfa for CLN2, vestronidase alfa for MPS VII, and sebelipase alfa for infantile-onset LAL-D-demonstrating that well-curated registries can serve as viable external controls for future LSD submissions. Gaucher disease offers a working template that, when extended across the LSD spectrum,..."

Biomarker • Journal • Review • Cardiovascular • CNS Disorders • Gaucher Disease • Genetic Disorders • Hypertension • Lysosomal Storage Diseases • Metabolic Disorders • Monoclonal Gammopathy • Movement Disorders • Oncology • Parkinson's Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Incidence and timing of diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2): A nationwide study using the French hospital discharge database. (PubMed, Eur J Paediatr Neurol) - "This is the first nationwide epidemiological assessment of CLN2 disease in France. The results demonstrate substantial diagnostic delays and disease burden, underscoring the need for earlier diagnosis and referral to expert centers to optimize care and offer genetic counseling to parents before conceiving subsequent offspring."

Journal • CNS Disorders • Critical care • Developmental Disorders • Epilepsy • Mental Retardation

Cerliponase Alfa Treatment in a Pre-Symptomatic Patient with Neuronal Ceroid Lipofuscinosis Type 2 CLN2 and Atypical Phenotype: A Case Report (SSIEM 2023) - No abstract available

Case report • Clinical • CNS Disorders

Rapid, accurate and comprehensive diagnostic method for the detection of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease using long-read third-generation sequencing technology (SSIEM 2023) - "Cerliponase alfa, the recombinant human TPP1, is the first and recently approved enzyme replacement therapy for the treatment of CLN2 disease... Targeted long-read third-generation sequencing technologies will provide a game-changing advantage for achieving a rapid, accurate, and comprehensive molecular diagnosis in order to start the needed treatments as early as possible."

CNS Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • TPP1

First in-human intracisternal dosing of RGX-181 (adeno-associated virus 9 / human tripeptidyl peptidase 1) for a 5-year-old child with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2): 6 month follow-up (SSIEM 2023) - "Treatment involves biweekly intracerebroventricular enzyme replacement therapy (ERT) with cerliponase alfa via an indwelling port...RGX-181 is a recombinant adeno-associated virus serotype 9 vector (AAV9) containing a human CLN2 expression cassette (AAV9.CB7.hCLN2) designed to induce sustained secretion of TPP1 enzyme in the CNS...Prednisone, tacrolimus, and sirolimus were administered per the protocol’s immunosuppressive regimen...Discussion/Conclusion First-in-human administration of RGX-181 has been well tolerated to date. Observation and data collection are ongoing."

Clinical • First-in-human • P1 data • CNS Disorders • Epilepsy • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • TPP1

Chest-sited intraventricular access devices for cerliponase alfa infusion in Batten disease at a single tertiary United Kingdom pediatric center. (PubMed, J Neurosurg Pediatr) - "Both devices had similar survival rates and incident and complication rates. Chest-sited devices can be considered a safe and effective alternative in this setting."

Journal • Anesthesia • CNS Disorders • Infectious Disease • Pediatrics

Treatment of Neuronal Ceroid Lipofuscinosis Type 2 with Cerliponase Alfa: A Systematic Review and Single-Arm Meta-Analysis of Two Studies. (PubMed, J Child Neurol) - "Significant heterogeneity was observed. Cerliponase alfa may improve clinical outcomes in children with CLN2, though adverse effects might be prevalent."

Journal • Retrospective data • Review • CNS Disorders • Dystonia • Epilepsy • Immunology • Movement Disorders • Rare Diseases • TPP1

Cerliponase alfa therapy leads to long-term seizure freedom in a patient with late infantile neuronal ceroid lipofuscinosis. (PubMed, Seizure) - No abstract available

Journal • CNS Disorders • Epilepsy

Management of positive cerebrospinal fluid cultures from intraventricular reservoirs of neuronal ceroid lipofuscinosis type 2 patients: one institution's experience. (PubMed, J Neurosurg Pediatr) - "At the authors' institution, we have found that in asymptomatic patients with frequently accessed ventricular reservoirs, positive CSF culture with low virulence skin flora was common. Rarely did positive cultures with common skin flora necessitate intervention. The authors' experience has shown that nonvirulent infection of ventricular reservoirs with low virulence skin flora can be monitored without intervention. This strategy reduces the risks of invasive surgery, prolonged antibiotic courses, and missed infusions."

Journal • CNS Disorders • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Case Report: The window that closed too soon: lessons from a late CLN2 diagnosis and death of a 9-year-old boy. (PubMed, Front Genet) - "Cerliponase alfa (known as Brineura) is an enzyme replacement therapy and has become increasingly important in treating CLN2 disease (late-infantile NCL), which is caused by a deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1)...It emphasizes how neurologists and pediatricians need to be more aware of NCLs as possible causes of developmental regression and early-onset epilepsy. Children with such presentations may benefit from earlier metabolic or enzyme testing, which could increase access to treatments that prolong life and change the disease's deadly course."

Journal • Alzheimer's Disease • Ataxia • CNS Disorders • Dementia • Epilepsy • Movement Disorders • Pediatrics • Rare Diseases • TPP1

Same-Day Approach for Combined Intravitreal and Intracerebroventricular Enzyme Replacement Therapy to Prevent Retinal Disease Progression in Children With Neuronal Ceroid Lipofuscinosis Type 2. (PubMed, Pediatr Neurol) - "We believe our pathway can be applied at all centers that are currently administering intracerebroventricular cerliponase alfa and that have the ophthalmologic expertise available to administer intravitreal injections."

Journal • Anesthesia • CNS Disorders • Ophthalmology • Pediatrics • Retinal Disorders • TPP1

LTS-101: An Intracerebroventricular Delivered AAV Gene Therapy Using a Novel Capsid Variant for the Treatment of CLN2 Batten Disease (ASGCT 2025) - "While bi-monthly infusions of recombinant human TPP1 (cerliponase alfa) to the brain have provided benefit to patients, significant disease burden remains and the therapy requires families relocate to infusion centers for the frequent, hours long, infusions... Preclinical studies in CLN2-/-mice and NHPs have established proof of concept for LTS-101 as a treatment for CLN2 disease. A definitive mouse pharmacology study and NHP GLP toxicology study are on-going. Clinical development planning is progressing in collaboration with world-leaders in CLN2 disease."

Gene therapy • CNS Disorders • Gene Therapies • Genetic Disorders • Pediatrics • TPP1

Novel surgical approach for intraventricular cerliponase alfa enzyme replacement therapy via central venous access device (CVAD) port in neuronal ceroid lipofuscinosis type 2 (CLN2) disease. (PubMed, Childs Nerv Syst) - "The use of an intraventricular access device connected to a CVAD allows for safe and efficacious long-term infusion of cerliponase alfa therapy and provides a more stable and well-tolerated alternative to scalp-based infusions."

Journal • CNS Disorders • Epilepsy • Genetic Disorders • Infectious Disease • TPP1

ORPHAN DRUGS IN ALZHEIMER'S DISEASE: CROSSROAD OF AMYLOID PATHOLOGY AND LYSOSOMAL STORAGE DISEASES (ADPD 2025) - "To test this hypothesis the effects of cerliponase alfa and taliglucerase alfa on A β accumulation in mouse hippocampal neurons (HT -22 neuronal cells) exposed to fAβ1-42 (a toxic fragment of full -length A β) and markers of autophagy -lysosome pathway related to AD were investigated. Therefore, we suggest that these orphan drugs could be considered promising novel therapeutics for neurodegenerative diseases in which autophagy pathways are impaired."

Alzheimer's Disease • CNS Disorders • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • ATG5 • GBA1 • mTOR