| Modality | Intervention | Route/dose | Evidence/outcomes (key quantitative results) | Safety highlights | Trial/Study ID (NCT if applicable) | Pub/registry URL + year | Citation ID |
|---|---|---|---|---|---|---|---|
| ERT | Cerliponase alfa (BMN 190, Brineura) | Intracerebroventricular; recommended 300 mg every other week in patients ≥2 years; infusion via implanted ventricular reservoir/catheter | Pivotal phase 1/2 study enrolled 24 patients; efficacy assessed against natural history using Motor-Language scale over 48+ weeks. Long-term clinical benefit summarized in reviews: at 300 mg every 2 weeks, 18/23 (78%) completing patients had slower-than-expected progression or stabilization after at least 96 weeks (median 116 weeks, range 96–145). In treated movement-disorder cohort, progression on UBDRS physical subscale slowed from 1.45 points/month before diagnosis to 0.44 points/month on treatment (p=0.019). | Frequent AEs in product information/clinical experience include pyrexia, convulsions, vomiting, device-related infection, hypersensitivity; device complications and meningitis are important risks. | NCT01907087 | ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT01907087 (2013); Brineura SmPC excerpt (2024 context); Neurology study https://doi.org/10.1212/WNL.0000000000209615 (2024) | (pqac-00000024, pqac-00000013, pqac-00000014, pqac-00000023, pqac-00000011) |
| ERT extension / long-term implementation | Cerliponase alfa long-term extension | Intracerebroventricular; extension after parent BMN190-201 study | Long-term efficacy/safety follow-up extended through Week 289/last observation; eligibility required prior completion of 48 weeks in parent trial. Represents real-world transition to chronic lifelong therapy. | Ongoing monitoring emphasizes reproductive precautions, clinical status, and Hamburg CLN2 rating scale eligibility thresholds. | NCT02485899 | ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT02485899 (2015) | (pqac-00000026) |
| ERT earlier-treatment cohort | Cerliponase alfa in pediatric patients <18 years | Intracerebroventricular; study initiated to begin treatment earlier in disease course | Trial identified in reviews as an earlier-treatment study following pivotal development program; intended to assess safety/tolerability/efficacy in pediatric patients <18 years. | Safety considerations as for Brineura: hypersensitivity, device-related complications, CNS infection monitoring. | NCT02678689 | ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT02678689 (2016) | (pqac-00000023, pqac-00000028) |
| Real-world ERT safety surveillance | Cerliponase alfa observational study in the US | Commercial cerliponase alfa plus administration kit; routine clinical use | Prospective observational cohort, estimated n=35, 10-year safety surveillance in U.S. practice. Secondary outcomes include hypersensitivity/anaphylaxis, serious cardiovascular AEs, device complications, and impact of severe SAEs on motor/language function. | Specifically designed to capture long-term real-world safety, including device-related complications and severe SAEs. | NCT04476862 | ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT04476862 (2020) | (pqac-00000029) |
| Real-world ERT in atypical CLN2 | Cerliponase alfa for atypical phenotypes | Intracerebroventricular; treatment duration 11–58 months in retrospective series | In 14 atypical patients, median age at first symptom 5.9 y, diagnosis 10.8 y, treatment start 11.7 y; motor-language score remained stable in 11/14, improved by 1 point in 1/14, declined by 1 point in 2/14. Supports use beyond classic phenotype. | 13 device-related infections in 8/14 patients (57%); 10 hypersensitivity reactions in 6/14 (43%). | Retrospective case series | https://doi.org/10.1177/0883073820977997 (2021) | (pqac-00000004, pqac-00000027) |
| Real-world post-marketing safety | Cerliponase alfa adverse-reaction surveillance | Post-marketing spontaneous reports (EudraVigilance) | Descriptive real-world pharmacovigilance analysis found reports more frequent in females (58.1%) and in children aged 3–11 years; most common events were pyrexia, device-related infection, vomiting, seizures/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. | Confirms known safety profile but highlights need for continued surveillance for device infection, ventriculitis, seizure-related events, and inflammatory CSF findings. | Post-marketing database study | https://doi.org/10.3390/ph17111513 (2024) | (pqac-00000003) |
| Gene therapy | AAVrh.10hCLN2 | Intraparenchymal brain administration via six burr holes to 12 brain sites; single administration | Phase 1/2 nonrandomized trial in 8 children with mild-moderate disease showed 1.3- to 2.6-fold increase in CSF TPP1, slower gray-matter loss in 4/7 by MRI, and 42.4% and 47.5% reduction in motor/language decline versus Weill Cornell and European natural-history cohorts, respectively. | Variety of expected AEs, none causing long-term disability; mild systemic anti-AAVrh.10 immune responses. Benefit was less than recombinant TPP1 ERT, indicating need for improved vector/delivery. | NCT01414985 | https://doi.org/10.1126/scitranslmed.abb5413 (2020); ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT01414985 (2011) | (pqac-00000006, pqac-00000024) |
| Preclinical/translation gene therapy | AAVrh.10hCLN2 intracisternal delivery | Intracisternal CSF delivery in nonhuman primates | IND-enabling study showed broad CNS distribution: CSF TPP1 reached 43–62% of normal human levels; >2x control brain TPP1 activity in 41–50% of treated brains, supporting less invasive CSF delivery for future trials. | No major behavioral/MRI/chemistry abnormalities; dorsal root ganglion mononuclear infiltrates/neuronal degeneration in 1/2 treated animals. | Preclinical safety/biodistribution | https://doi.org/10.1089/hum.2023.067 (2023) | (pqac-00000001) |
| Ocular ERT | Intravitreal rhTPP1 for CLN2 retinopathy | Right eye intravitreal injections; 0.2 mg in 0.05 mL; 8 weekly injections with follow-up 12–18 months, left eye untreated paired control | First-in-human controlled study in 8 children. No severe adverse reactions. Mean baseline PMV 1.28 mm3 (right) vs 1.27 mm3 (left). Three youngest patients had progressive bilateral thinning; in those 3, PMV loss was slower in treated vs untreated eye (p=0.000042, p=0.0011, p=0.00022). Mean decline among progressors: 0.168 mm3/year treated vs 0.254 mm3/year untreated. | No severe ocular AEs (no uveitis, raised IOP, media opacity). Momentary CRA occlusion after injection in 2 severe-vasculopathy patients relieved by paracentesis; one anesthesia-related laryngospasm. | First-in-man prospective controlled study | https://doi.org/10.1038/s41433-023-02859-4 (2024) | (pqac-00000015, pqac-00000016, pqac-00000017, pqac-00000018) |
| Ocular ERT trial | Intravitreal cerliponase alfa to prevent retinal progression | Intravitreal injection under sedation every 4 weeks for 24 months, then 3-year monitoring extension | Active phase 1/2 study, planned n=5, testing whether ocular ERT can stabilize fundoscopic severity score and OCT central retinal thickness in young children already receiving intraventricular ERT. | Primary endpoint is unacceptable treatment-related toxicity (Grade 3+); DSMB monitored. | NCT05152914 | ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05152914 (2021) | (pqac-00000022) |
| Ocular gene therapy | TTX-381 for ocular manifestations of CLN2 | Gene therapy; route not specified in provided excerpt (first-in-human ocular study) | Recruiting phase 1/2 dose-escalation study evaluating safety/tolerability of gene therapy for CLN2 ocular disease; planned enrollment 16. | Early-phase safety-focused study; detailed AE/outcome data not yet available in provided context. | NCT05791864 | ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05791864 (2023) | (pqac-00000000) |
| Supportive / multidisciplinary care | Antiseizure therapy, rehabilitation, device care, family support, ophthalmic monitoring | Symptom-directed; multidisciplinary | Expert consensus recommends multidisciplinary management, focusing on seizure control, quality of life, family support, EEG/MRI/genetic/biochemical monitoring, and management of ventricular access devices. Developmental and QoL studies show substantial burden and functional decline, supporting supportive care even with disease-modifying therapy. | Supportive care must address infections, feeding/mobility decline, anesthesia burden, and caregiver strain. | Consensus / observational care pathway | https://doi.org/10.1055/s-0043-1761434 (2023); ClinicalTrials.gov NCT03862274 (2018) | (pqac-00000008, pqac-00000025) |


*Table: This table summarizes disease-modifying and supportive treatment strategies for CLN2 disease, including pivotal and ongoing clinical trials, routes and dosing, quantitative outcomes, and key safety issues. It is useful for comparing established intracerebroventricular enzyme replacement with emerging brain and ocular gene/enzyme therapies and real-world implementation evidence.*