Brineura (cerliponase alfa) / BioMarin - LARVOL DELTA

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

Real-world clinical outcomes of patients with CLN2 disease treated with cerliponase alfa. (PubMed, Front Neurol) - "No ERT-treated patients died. Cerliponase alfa for real-world CLN2 disease treatment slowed decline in motor and language function and demonstrated an acceptable safety profile."

Clinical data • Journal • Real-world evidence • CNS Disorders

Progress in gene therapy for CLN2 Batten disease related retinopathy (ARVO 2025) - "The gene encodes TPP1, a lysosomal enzyme, that permits clearance of toxic lipofuschin particularly in neurons.The disease typically presents with loss of perifoveal ellipsoid at the age of 3-4 years progressing to loss of sub-foveal ellipsoid, and subsequent centripetal spread throughout the fundus; complete vision loss typically occurs by the age of 7-8 years.Intracerebroventricular infusions of the recombinent pro-enzyme rhTPP1 - cerliponase alfa - now mean that children are surviving the disease, but continue to go blind. Our previous work (ARVO poster 2023) has demonstrated intravitreal enzyme replacement slows the progress of decline which maybe dose dependent but studies of the frequency of injection and dose escalation are still required.At ARVO 2024 we presented interim data from the RGX-381 study of ocular CLN2 gene replacement therapy based on the initial 4 patients recruited up to day 180 follow-up...This programme has now transferred ownership to Tern..."

Gene therapy • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • TPP1

Enzyme Replacement Therapy in CLN2-Associated Retinopathy. (PubMed, Klin Monbl Augenheilkd) - P1/2 | "In 2017, an intracerebroventricular enzyme replacement therapy (ERT) using recombinant human TPP1 (rhTPP1), cerliponase alfa, was approved as a disease-modifying treatment for CLN2 disease...This could be particularly relevant for those patients who were started on intracerebroventricular ERT early and still have good motor and language function. For this patient population, intravitreal ERT could be a valuable bridging therapy until other therapies such as gene therapy become available."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Epilepsy • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • TPP1

Speech, Language and Non-verbal Communication in CLN2 and CLN3 Batten Disease. (PubMed, J Inherit Metab Dis) - "Challenging behaviours were common in CLN3 (11/17, 65%), but less frequent in CLN2 (4/16, 25%) disease. Individuals with Batten disease require tailored speech therapy incorporating communication partner training utilising environment adaptations and informal communication behaviours."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Five-year Seizure Outcomes of Pediatric NCL2 Patients Treated with Cerliponase Alfa (AES 2024) - "Patients with NCL2 present with seizures of varying semiology which progresses to refractory epilepsy. Based on this case series, cerliponase alfa infusions improve the seizure burden of patients with NCL2 initially; however, patients show evidence of disease progression after several years on the therapy."

Clinical • CNS Disorders • Developmental Disorders • Epilepsy • Movement Disorders • Pediatrics • TPP1

Adverse Reactions to the Orphan Drug Cerliponase Alfa in the Treatment of Neurolipofuscinosis Type 2 (CLN2). (PubMed, Pharmaceuticals (Basel)) - "The most common adverse reactions were, in decreasing order, fever/pyrexia, device-related infection, vomiting, seizures/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. The results confirm the safety profile of cerliponase alfa established with pre-registration clinical studies but suggest the need for further studies to investigate the occurrence of adverse reactions, as possible predictive prognostic markers, in more depth."

Journal • Orphan drug • CNS Disorders • Epilepsy • Infectious Disease • Respiratory Diseases • TPP1

Psychometric Validation of the CLN2 Quality of Life Questionnaire in Participants with CLN2 Disease Treated with Cerliponase Alfa. (PubMed, Healthcare (Basel)) - "This study is the first to validate the CLN2 QoL and to estimate the CID of this instrument in CLN2 patients. Our results show good validity and reliability of this tool."

HEOR • Journal • CNS Disorders • Epilepsy • Pediatrics

Peripapillary Retinal Nerve Fiber Layer (pRNFL) Thickness - A Novel Biomarker of Neurodegeneration in Late-Infantile CLN2 Disease. (PubMed, Eye Brain) - "All patients received 300 mg of intracerebroventricular enzyme replacement treatment (cerliponase alfa) once every two weeks...Repeated measurements indicated decreases in pRNFL thickness over time in most patients. Patients with late-infantile CLN2 disease exhibit early onset progressive pRNFL loss regardless of outer retinal degeneration, highlighting the potential of pRNFL as an independent ocular biomarker for retinal pathology in late-infantile CLN2 disease."

Biomarker • Journal • Anesthesia • CNS Disorders • Ophthalmology • Pediatrics

Cerliponase alfa decreases Aβ load and alters autophagy- related pathways in mouse hippocampal neurons exposed to fAβ1-42. (PubMed, Life Sci) - "Furthermore, exposure to CER and fAβ1-42 induced the autophagy-regulatory/related pathways in HT-22 cells and exposure to CER alone increased sirtuin-1 activity. Based on the present findings, we suggest that augmentation of TPP1 with enzyme replacement therapy may be a potential therapeutic option for the treatment of AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • ATG5 • BECN1 • SQSTM1 • TPP1

LATE INFANTILE NEURONAL CEROID LIPOFUSCINOSIS TYPE 2 (CLN2): A MOSCOW CASE SERIES. (SSIEM 2024) - "All patients received Cerliponase alfa ERT, beginning at a mean age of 49 months (range 27–61 months)... In conclusion, our cohort highlights CLN2 disease's key features and provides additional EEG phenotypic data and insights into ERT efficacy for both symptomatic and asymptomatic patients."

Clinical • CNS Disorders • Developmental Disorders • Epilepsy • Lysosomal Storage Diseases • Metabolic Disorders • Ophthalmology • Rare Diseases • TPP1

SEIZURES AND MOVEMENT DISORDERS IN PATIENTS WITH CLN2 DISEASE TREATED WITH CERLIPONASE ALFA IN THE REAL-WORLD SETTING (SSIEM 2024) - "This analysis provides the first comprehensive description of the time course of seizures and movement disorders in a cohort of CLN2 disease patients receiving treatment with cerliponase alfa in the real-world setting."

Clinical • Real-world • Real-world evidence • Ataxia • CNS Disorders • Dystonia • Epilepsy • Movement Disorders • TPP1

IMPACT OF CERLIPONASE ALFA ON LIPIDOMIC CSF PROFILES IN CLN2 PATIENTS. (SSIEM 2024) - "In conclusion, the lipid profile of ventricular CSF in CLN2 patients differs from that of controls. Cerliponase alfa treatment can reverse some of these effects. Future studies aim to confirm results obtained so far with ventricular CSF of control patients."

Clinical • Ataxia • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Movement Disorders • Pediatrics • TPP1