Development of the “Hamburg Best Practice Guidelines for ICV−Enzyme Replacement therapy (ERT) in CLN2 Disease” Based on 6 Years Treatment Experience in 48 Patients

Schwering, Christoph; Kammler, Gertrud; Wibbeler, Eva; Martin, Coralie; Knobloch, J; Nickel, Miriam; Denecke, Jonas; Baehr, Michael; Schulz, Angela

doi:10.1177/0883073821989154

Cited by 9 publications

(5 citation statements)

References 18 publications

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“…The enzyme is administered directly to the CNS via an intra cerebro-ventricular catheter every 2 weeks. The safety of this approach is well documented by the most expert group with this procedure (173). As for its efficacy there is good evidence that disease progression is slowed down over a 4 year period, as compared with historical untreated controls (174,175).…”

Section: Complementation Therapymentioning

confidence: 99%

Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview

Simonati

Williams

2022

Front. Neurol.

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The main aim of this review is to summarize the current state-of-art in the field of childhood Neuronal Ceroid Lipofuscinosis (NCL), a group of rare neurodegenerative disorders. These are genetic diseases associated with the formation of toxic endo-lysosomal storage. Following a brief historical review of the evolution of NCL definition, a clinically-oriented approach is used describing how the early symptoms and signs affecting motor, visual, cognitive domains, and including seizures, may lead clinicians to a rapid molecular diagnosis, avoiding the long diagnostic odyssey commonly observed. We go on to focus on recent advances in NCL research and summarize contributions to knowledge of the pathogenic mechanisms underlying NCL. We describe the large variety of experimental models which have aided this research, as well as the most recent technological developments which have shed light on the main mechanisms involved in the cellular pathology, such as apoptosis and autophagy. The search for innovative therapies is described. Translation of experimental data into therapeutic approaches is being established for several of the NCLs, and one drug is now commercially available. Lastly, we show the importance of palliative care and symptomatic treatments which are still the main therapeutic interventions.

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Section: Complementation Therapymentioning

confidence: 99%

Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview

Simonati

Williams

2022

Front. Neurol.

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“…Similarly, fibroblasts from patients with late-infantile NCL (CLN2) showed alterations in the FA composition of PL, including PUFA [ 86 ]. A biomarker would be extremely helpful to establish an early diagnosis in CLN2, as the early stage is uncharacteristic with single seizures and mild developmental delay, but has the option of enzyme replacement therapy (ERT) by an intraventricular device [ 87 ].…”

Section: Lipid*omic*s In Rare Diseasesmentioning

confidence: 99%

Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases

Zandl-Lang

Plecko

Köfeler

2023

IJMS

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Even though the application of Next-Generation Sequencing (NGS) has significantly facilitated the identification of disease-associated mutations, the diagnostic rate of rare diseases is still below 50%. This causes a diagnostic odyssey and prevents specific treatment, as well as genetic counseling for further family planning. Increasing the diagnostic rate and reducing the time to diagnosis in children with unclear disease are crucial for a better patient outcome and improvement of quality of life. In many cases, NGS reveals variants of unknown significance (VUS) that need further investigations. The delineation of novel (lipid) biomarkers is not only crucial to prove the pathogenicity of VUS, but provides surrogate parameters for the monitoring of disease progression and therapeutic interventions. Lipids are essential organic compounds in living organisms, serving as building blocks for cellular membranes, energy storage and signaling molecules. Among other disorders, an imbalance in lipid homeostasis can lead to chronic inflammation, vascular dysfunction and neurodegenerative diseases. Therefore, analyzing lipids in biological samples provides great insight into the underlying functional role of lipids in healthy and disease statuses. The method of choice for lipid analysis and/or huge assemblies of lipids (=lipidome) is mass spectrometry due to its high sensitivity and specificity. Due to the inherent chemical complexity of the lipidome and the consequent challenges associated with analyzing it, progress in the field of lipidomics has lagged behind other omics disciplines. However, compared to the previous decade, the output of publications on lipidomics has increased more than 17-fold within the last decade and has, therefore, become one of the fastest-growing research fields. Combining multiple omics approaches will provide a unique and efficient tool for determining pathogenicity of VUS at the functional level, and thereby identifying rare, as well as novel, genetic disorders by molecular techniques and biochemical analyses.

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“…Reports from the literature show a low rate of device-related complications in patients with CLN2. 8,47 A retrospective evaluation of 48 patients with CLN2 receiving more than 3,000 sessions of ERT through ICV device reported an infection rate of 0.33 and 0.27% of non-infectious adverse events. 47 In the clinical trial with cerliponase α, 8% of the study population had an infection related to the device.…”

Section: Enzyme Replacement Therapymentioning

confidence: 99%

“…8,47 A retrospective evaluation of 48 patients with CLN2 receiving more than 3,000 sessions of ERT through ICV device reported an infection rate of 0.33 and 0.27% of non-infectious adverse events. 47 In the clinical trial with cerliponase α, 8% of the study population had an infection related to the device. 8 In this case, the best approach is to temporarily suspend the ERT administration, begin antibiotic treatment, and change the device (consensus; LE: 1b).…”

Section: Enzyme Replacement Therapymentioning

confidence: 99%

“…The essential devices for the proper application are a permanent ICV infusion catheter (Ommaya type) and an infusion pump for a syringe (consensus; LE: 5). A Rickham ICV reservoir can also be used, 47 and they are both available in Brazil. A child neurologist, a neurosurgeon, a pediatrician, and a nurse should be involved in the team for the infusion (consensus; LE: 5).…”

Section: Enzyme Replacement Therapymentioning

confidence: 99%

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Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group

et al. 2023

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Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigate and confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients.

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Development of the “Hamburg Best Practice Guidelines for ICV−Enzyme Replacement therapy (ERT) in CLN2 Disease” Based on 6 Years Treatment Experience in 48 Patients

Cited by 9 publications

References 18 publications

Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview

Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview

Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases

Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group

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