Another month has passed, which means it’s time for research updates. BDSRA Foundation’s Head of Research & Medical Affairs Dr. Ineka Whiteman breaks down Batten disease clincial program updates, resources, and publocation summaries in her monthly column, as seen in BDSRA’s monthly newsletter, The Illuminator.
CLINICAL PROGRAM UPDATES
Clinical Trial Tracker
Keep up to date with the latest clinical trial and natural history study news with our Clinical Studies Chart on the BDSRA Foundation’s website. Check it out by clicking here.
Elpida Therapeutics – CLN7 Gene Therapy Program Update
On January 18, Elpida Therapeutics held an online meeting for the CLN7 disease community to discuss the AAV-based gene therapy (AAV9/MFSD8) program currently in Phase 1 trial for the treatment of CLN7 disease, and Eplida’s plans to move to the next phase of clinical trials. The meeting was attended by families, doctors, scientists, and patient advocacy groups from all over the world. The primary aims of the meeting were (1) how to most effectively identify and connect with CLN7 disease patients and their families globally, and (2) to discuss the potential design, strategy, and initiation of a retrospective and prospective natural history study, a vital clinical trial component for evaluating the efficacy of the investigational gene therapy. Elpida Therapeutics is working hard to develop a standardized data collection approach and will hold another meeting with families in the very near future.
For further information on the CLN7 gene therapy program and to stay up-to-date with program developments, please reach out to Souad Messahel, Head of Clinical Operations at Souad@elpidatx.com.
A copy of the presentation from the January 18 meeting can be downloaded here.
Neurogene – CLN5 Gene Therapy Program Updates
On December 19, 2023, Neurogene released the following announcement:
“We are thrilled to share that the merger that we announced in July of this year between Neurogene and Neoleukin Therapeutics is now complete, which secures the funding we need to advance our mission of bringing life-changing genetic medicines to patients and families impacted by devastating neurological diseases. In connection with this merger, we are moving from a privately held company to a public traded company, and will begin trading today on the NASDAQ under the ticker ‘NGNE’.”
Further to this, on January 5, Neurogene announced the completion of enrollment of Cohorts 1 and 2 in the ongoing Phase 1/2 clinical trial for CLN5 Batten disease, with interim clinical data expected in the second half of 2024. Neurogene is currently enrolling a final higher dose cohort for this study.
In the fourth quarter of 2023, Neurogene completed a positive meeting with the FDA regarding the future potency assay for batches of the ‘NGN-101’ study drug. The FDA accepted Neurogene’s proposed potency assay strategy and provided alignment with the testing approach, which will allow the release of all future NGN-101 batches.
To enable advancement into a registration study, Neurogene is collecting and analyzing natural history data for CLN5 Batten disease and planning to request a clinical/regulatory strategy meeting with the FDA in the second half of 2024. The focus of this meeting will be to align with the FDA on the expected clinical requirements to support a streamlined registration pathway, which will be necessary to move this program forward into a pivotal clinical trial.
Read the full press release here.
CLN5 Disease Natural History Study
In relation to these CLN5 gene therapy program updates, BDSRA would like to remind our community that the natural history study for CLN5 disease, mentioned above, is still open for recruitment and seeking participants. This international study is open to all individuals with a genetic diagnosis of CLN5 disease and where disease onset occurred at the age of five years or younger. Current and bereaved families affected by CLN5 disease are encouraged to participate.
For further information, please get in touch with the recruitment site – the University of Rochester Batten Center (URBC) – or reach out to Dr. Ineka Whiteman, BDSRA’s Head of Research & Medical Affairs via email at research@bdsraaustralia.org.
Beyond Batten Disease Foundation/Theranexus – Batten-1 Program for CLN3 Disease
Phase 3 trial of Batten-1 for treatment of CLN3 disease
A reminder to families: Enrolment for the international Batten-1 (miglustat) Phase 3 study is expected to commence in the coming months. This study is open to participants worldwide, with study sites across the U.S., Europe, the U.K., and Australia.
To ensure you are kept up-to-date with the latest study information and developments, you can join the Beyond Batten Disease Foundation (BBDF) family mailing list by emailing Mary Beth Kiser, President and CEO at BBDF, at mbkiser@beyondbatten.org or Dr Ineka Whiteman at research@bdsraaustralia.org.
CONFERENCE NEWS
WORLD Symposium – Free Registration for Families
February 4-9, 2024
Manchester Grand Hyatt San Diego, San Diego, CA, USA
WORLDSymposium is an annual research conference dedicated to lysosomal diseases (WORLD actually stands for We’re Organizing Research on Lysosomal Diseases). This meeting attracts researchers, patient advocacy groups, clinicians, industry partners, and all others who are interested in learning about the latest discoveries and clinical advances in lysosomal diseases, including Batten disease.
COMPLIMENTARY REGISTRATION FOR PATIENTS AND PATIENT FAMILY MEMBERS
To make the 2024 Annual Scientific Meetings accessible for lysosomal disease patients and their families, WORLDSymposium is offering complimentary registration (for in-person and/or online attendance) to all lysosomal disease patients 18 and over. Immediate adult family members (18 and over) may also be registered. For more information and registration links, click here.
The WORLDSymposium 2024 daily programs can be viewed here.
NCL2025 International Congress
Held every two years, the International Congress on Neuronal Ceroid Lipofuscinosis (NCL Congress) is the premier conference for NCL basic, translational, and clinical research. This meeting is primarily geared toward researchers, clinicians, industry partners, and patient groups. However, international families are also warmly invited to attend.
NCL2025 will be held in Australia in late 2025, with details to be announced in the coming months. To assist with planning, the local Congress Organising Committee invites all potential attendees (researchers, clinicians, industry partners, patient groups, and families) to fill in this expression of interest survey at your earliest convenience.
We hope to see you Down Under!
FAMILY REGISTER
Have you joined the Register yet?
In recent months, we’ve had a wonderful response to our calls for families to join our Family Register. Let’s keep it going!
The BDSRA Foundation Family Register is a vital tool that enables us to keep you informed of ongoing Batten disease research, including future clinical research opportunities.
The Register also enables the BDSRA Foundation to better understand the prevalence of Batten disease, including the different subtypes and geographical locations. This helps us tailor our education and support activities according to the needs of our families. The Register is open to all current and bereaved families in the U.S. and internationally.
The information collected in this form is kept STRICTLY CONFIDENTIAL. Your involvement in this survey is entirely voluntary, and you may request to be removed from the list at any time. The form takes just a few minutes to complete and can be accessed by clicking here.
Thank you for participating in this important initiative!
PUBLICATION HIGHLIGHTS: December 2023-January 2024
First in man study of intravitreal tripeptidyl peptidase 1 for CLN2 retinopathy
Wawrzynski J, et al. Eye (Lond). 2023 Dec 4. Online ahead of print.
ABSTRACT
Background/objectives: CLN2 Batten Disease is a fatal neurodegenerative condition of childhood associated with retinal dystrophy and blindness. Intracerebroventricular infusion of rhTPP1 greatly slows the rate of neurodegenerative decline but not retinopathy. Intravitreal rhTPP1 is known to slow retinal degeneration in a canine model of CLN2. We report a first-in-man controlled clinical trial of intravitreal rhTPP1 for CLN2-associated retinal dystrophy.
Results: No severe adverse reactions (uveitis, raised IOP, media opacity) occurred. The mean baseline PMV was 1.28 mm3(right), 1.27 mm3(left). 3 of the youngest patients exhibited bilateral progressive retinal thinning (p < 0.05), whereas retinal volume was stable in the remaining 5 patients. In the 3 patients undergoing retinal degeneration, the rate of PMV loss was slower in the treated vs. untreated eye (p = 0.000042, p = 0.0011, p = 0.00022).
Conclusions: Intravitreal rhTPP1 appears to be a safe and effective treatment for CLN2-related retinopathy however commencement of treatment early in the course of disease is more likely to be efficacious.
Access the full article here.
REVIEW – Intravitreal enzyme replacement for inherited retinal diseases
Rodriguez-Martinez, A. et al. Curr Opin Ophthalmol. 2023 Dec 27. Online ahead of print.
ABSTRACT
Purpose of review: This paper provides an update on intravitreal (IVT) enzyme replacement therapy (ERT) in metabolic retinal diseases; particularly neuronal ceroid lipofuscinosis type 2 (CLN2) also known as Batten disease.
Recent findings: ERT is being explored in CLN2-related Batten disease, a fatal neurodegenerative condition associated with retinopathy and blindness that is caused by the deficiency of lysosomal enzyme TPP1. Cerliponase alfa, a recombinant human tripeptidyl-peptidase1 (rhTPP1) administered by intraventricular infusions has been demonstrated to slow the rate of neurodegenerative decline but not retinopathy. A preclinical study of IVT rhTPP1 in a CLN2 canine model demonstrated efficacy in preserving retinal function and retinal morphology shown on histology. More recently, intravitreal (IVT) administration of rhTPP1 was reported in a first-in-human compassionate use study. Patients received 12-18 months of 8-weekly IVT ERT (0.2 mg rhTPP-1 in 0.05 ml) in one eye. No significant ocular adverse reactions were reported. Treatment decreased the rate of retinal thinning but modestly.
Summary: The evidence suggests that IVT ERT with rhTPP1 may be a safe and effective treatment for CLN2 retinopathy. However, the optimal dosage and frequency to achieve the best possible outcomes require further investigation as does patient selection.
Access the full article here.
Developmental skills and neurorehabilitation for children with Batten disease: A Retrospective chart review of a comprehensive Batten clinic
Bican, R. et al. Pediatr Neurol. 2023 Dec 5:152:107-114. Online ahead of print.
ABSTRACT
Background: Batten disease is a rare, progressive neurogenetic disorder composed of 13 genotypes that often presents in childhood. Children present with seizures, vision loss, and developmental regression. Neurorehabilitation services (i.e., physical therapy, occupational therapy, and speech-language therapy) can help improve the quality of life for children and their families. Owing to the rarity of Batten disease, there are no standardized clinical recommendations or outcome assessments. To describe developmental profiles, current dose of neurorehabilitation, and outcome assessments used clinically for children diagnosed with Batten disease.
Results: Across CLN subtypes, most children experienced vision impairments (61%) and seizures (68%). Most children demonstrated delays in fine motor (65%), gross motor (80%), cognitive (63%), and language skills (83%). The most common frequency of neurorehabilitation was weekly (42% to 43%). Two standardized outcome assessments were used to track developmental outcomes: Peabody Developmental Motor Scales, second edition (30% of children completed this assessment) and Preschool Language Scales, fifth edition (27.4% of children completed this assessment).
Conclusions: Neurorehabilitation professionals should understand the clinical features and prognosis for children with Batten disease. The child’s clinical features and family preferences should guide the rehabilitation plan of care. Future work needs to be completed to define dosing parameters and validate outcome assessments for neurorehabilitation services.
Access the full text here.
Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study.
Schulz A, et al. Lancet Neurol. 2024 Jan;23(1):60-70. doi: 10.1016/S1474-4422(23)00384-8.
ABSTRACT
Background: Cerliponase alfa is a recombinant human tripeptidyl peptidase 1 (TPP1) enzyme replacement therapy for the treatment of neuronal ceroid lipofuscinosis type 2 (CLN2 disease), which is caused by mutations in the TPP1 gene. We aimed to determine the long-term safety and efficacy of intracerebroventricular cerliponase alfa in children with CLN2 disease.
Findings: Between Sept 13, 2013, and Dec 22, 2014, 24 participants were enrolled in the primary study (15 female and 9 male). Of those, 23 participants were enrolled in the extension study, conducted between Feb 2, 2015, and Dec 10, 2020, and received 300 mg cerliponase alfa for a mean of 272·1 (range 162·1-300·1) weeks. 17 participants completed the extension and six discontinued prematurely. Treated patients were significantly less likely than historical untreated controls to have an unreversed 2-point decline or score of 0 in the combined motor and language domains (hazard ratio 0·14, 95% CI 0·06 to 0·33; p<0·0001). All participants experienced at least one adverse event and 21 (88%) experienced a serious adverse event; nine participants experienced intracerebroventricular device-related infections, with nine events in six participants resulting in device replacement. There were no study discontinuations because of an adverse event and no deaths.
Interpretation: Cerliponase alfa over a mean treatment period of more than 5 years was seen to confer a clinically meaningful slowing of decline of motor and language function in children with CLN2 disease. Although our study does not have a contemporaneous control group, the results provide crucial insights into the effects of long-term treatment.
Access the full article here.
REVIEW – Cerliponase alfa and neuronal ceroid lipofuscinosis type 2: long-term outcomes and lessons for future research.
Boustany RM. Lancet Neurol. 2024 Jan;23(1):5-7. No abstract available.
Access the full article here.
Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): an auditory evoked potential study of the duration-evoked mismatch negativity (MMN)
Brima, T. et al. J Neurodev Disord. 2024 Jan 6;16(1):3.
ABSTRACT
Background: We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of “duration” processing. Given decrements in auditory processing abilities associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event-related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials.
Results: Data from individuals with CLN3 disease (N = 21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N = 41; ages 6-26 years).
Conclusions: Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.
Access the full article here.
RELATED MEDIA ARTICLE – Researchers find possible neuromarker for ‘juvenile-onset’ Batten disease
Read the article here.
Characterization of two human induced pluripotent stem cell lines derived from Batten disease patient fibroblasts harbouring CLN5 mutations
Ofrim, M. et al. Stem Cell Res. 2024 Feb:74:103291. Epub 2023 Dec 18.
ABSTRACT
The neuronal ceroid lipofuscinoses (NCLs) are a group of common inherited neurodegenerative disorders of childhood. All forms of NCLs are life-limiting with no curative treatments. Most of the 13 NCL genes encode proteins residing in endolysosomal pathways, such as CLN5, a potential lysosomal enzyme. Two induced pluripotent stem cell lines (hiPSCs) were generated from skin fibroblasts of CLN5 disease patients via non-integrating Sendai virus reprogramming. They demonstrate typical stem cell morphology, express pluripotency markers, exhibit trilineage differentiation potential, and also successfully differentiate into neurons. These hiPSCs represent a potential resource to model CLN5 disease in a human context and investigate potential therapies.
Access the full article here.
Haploidentical haematopoietic stem cell transplantation combined with post-transplant cyclophosphamide in neuronal ceroid lipofuscinosis: Experience in eight patients
Song Z, et al. Med Clin (Barc). 2023 Dec 2:S0025-7753(23)00523-7.
ABSTRACT
Background: Neuronal ceroid lipofuscinoses (NCLs) are rare lysosomal storage disorders characterized by progressive mental retardation and motor developmental regression and myoclonic seizures. Hematopoietic stem cell transplantation (HSCT) has been suggested to be used in the treatment of lysosomal disorders and brain damage caused by a deficiency of soluble lysosomal enzymes. There are no previous reports on treating NCLs with HSCT in China.
Results: From January 2018 to May 2019, the haplo-HSCT followed by PT/Cy on eight NCL pediatric patients was performed. The median age was 4.5 years (ranging from 2.8 to 7 years). The donors were their haploidentical HLA-matched parents, as no identically matched donors were found. The median nucleated cell count was 25.37 (10-34.41)×108/kg, and the median CD34+ count was 13.7 (8.95-22)×106/kg. Neutrophil reconstitution occurred 12 days (11-14 days) after transplantation, and the median platelet reconstitution time was 12 days (9-14 days) after transplantation. All patients achieved full donor chimerism and did not develop Grade II-IV acute GvHD or chronic GvHD after transplantation. The median follow-up period was 2.2 (1.5-2.6) years. All patients are still alive at present and develop no severe transplantation-related complications. The mental motor disorders, myoclonic seizures, and vision loss of all patients continued to progress. However, the progression slowed at 12 months after transplantation.
Conclusion: This study demonstrated that it is safe and efficacious to treat NCLs with haplo-HSCT. Transplantation should be performed at an early stage for the survival quality of pediatric patients.
Access the full article here.
CLN3 deficiency leads to neurological and metabolic perturbations during early development
Heins-Marroquin, U. et al. Life Sci Alliance. 2024 Jan 9;7(3):e202302057.
ABSTRACT
Juvenile neuronal ceroid lipofuscinosis (or Batten disease) is an autosomal recessive, rare neurodegenerative disorder that affects mainly children above the age of 5 yr and is most commonly caused by mutations in the highly conserved CLN3 gene. Here, we generated cln3 morphants and stable mutant lines in zebrafish. Although neither morphant nor mutant cln3 larvae showed any obvious developmental or morphological defects, behavioral phenotyping of the mutant larvae revealed hyposensitivity to abrupt light changes and hypersensitivity to pro-convulsive drugs. Importantly, in-depth metabolomics and lipidomics analyses revealed significant accumulation of several glycerophosphodiesters (GPDs) and cholesteryl esters, and a global decrease in bis(monoacylglycero)phosphate species, two of which (GPDs and bis(monoacylglycero)phosphates) were previously proposed as potential biomarkers for CLN3 disease based on independent studies in other organisms. We could also demonstrate GPD accumulation in human-induced pluripotent stem cell-derived cerebral organoids carrying a pathogenic variant for CLN3 Our models revealed that GPDs accumulate at very early stages of life in the absence of functional CLN3 and highlight glycerophosphoinositol and BMP as promising biomarker candidates for pre-symptomatic CLN3 disease.
Access the full article here.
Mechanisms regulating the intracellular trafficking and release of CLN5 and CTSD
Huber, RJ. et al. Traffic. 2024 Jan;25(1):e12925.
ABSTRACT
Ceroid lipofuscinosis neuronal 5 (CLN5) and cathepsin D (CTSD) are soluble lysosomal enzymes that also localize extracellularly. In humans, homozygous mutations in CLN5 and CTSD cause CLN5 disease and CLN10 disease, respectively, which are two subtypes of neuronal ceroid lipofuscinosis (commonly known as Batten disease). The mechanisms regulating the intracellular trafficking of CLN5 and CTSD and their release from cells are not well understood. Here, we used the social amoeba Dictyostelium discoideum as a model system to examine the pathways and cellular components that regulate the intracellular trafficking and release of the D. discoideum homologs of human CLN5 (Cln5) and CTSD (CtsD). We show that both Cln5 and CtsD contain signal peptides for secretion that facilitate their release from cells. Like Cln5, extracellular CtsD is glycosylated. In addition, Cln5 release is regulated by the amount of extracellular CtsD. Autophagy induction promotes the release of Cln5, and to a lesser extent CtsD. Release of Cln5 requires the autophagy proteins Atg1, Atg5, and Atg9, as well as autophagosomal-lysosomal fusion. Atg1 and Atg5 are required for the release of CtsD. Together, these data support a model where Cln5 and CtsD are actively released from cells via their signal peptides for secretion and pathways linked to autophagy. The release of Cln5 and CtsD from cells also requires microfilaments and the D. discoideum homologs of human AP-3 complex mu subunit, the lysosomal-trafficking regulator LYST, mucopilin-1, and the Wiskott-Aldrich syndrome-associated protein WASH, which all regulate lysosomal exocytosis in this model organism. These findings suggest that lysosomal exocytosis also facilitates the release of Cln5 and CtsD from cells. In addition, we report the roles of ABC transporters, microtubules, osmotic stress, and the putative D. discoideum homologs of human sortilin and cation-independent mannose-6-phosphate receptor in regulating the intracellular/extracellular distribution of Cln5 and CtsD. In total, this study identifies the cellular mechanisms regulating the release of Cln5 and CtsD from D. discoideum cells and provides insight into how altered trafficking of CLN5 and CTSD causes disease in humans.
Read the full article here.
CLN2 disease resulting from a novel homozygous deep intronic splice variant in TPP1 discovered using long-read sequencing
Steigerwald, C. et al. Mol Genet Metab. 2023 Dec;140(4):107713.
ABSTRACT
Neuronal ceroid lipofuscinosis type 2 (CLN2) is an autosomal recessive neurodegenerative disorder with enzyme replacement therapy available. We present two siblings with a clinical diagnosis of CLN2 disease, but no identifiable TPP1 variants after standard clinical testing. Long-read sequencing identified a homozygous deep intronic variant predicted to affect splicing, confirmed by clinical DNA and RNA sequencing. This case demonstrates how traditional laboratory assays can complement emerging molecular technologies to provide a precise molecular diagnosis.
Access the full article here.
Loss of Depalmitoylation Disrupts Homeostatic Plasticity of AMPARs in a Mouse Model of Infantile Neuronal Ceroid Lipofuscinosis.
Koster KP, et al. J Neurosci. 2023 Dec 6;43(49):8317-8335.
ABSTRACT
Protein palmitoylation is the only reversible post-translational lipid modification. Palmitoylation is held in delicate balance by depalmitoylation to precisely regulate protein turnover. While over 20 palmitoylation enzymes are known, depalmitoylation is conducted by fewer enzymes. Of particular interest is the lack of the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1) that causes the devastating pediatric neurodegenerative condition infantile neuronal ceroid lipofuscinosis (CLN1). While most of the research on Ppt1 function has centered on its role in the lysosome, recent findings demonstrated that many Ppt1 substrates are synaptic proteins, including the AMPA receptor (AMPAR) subunit GluA1. Still, the impact of Ppt1-mediated depalmitoylation on synaptic transmission and plasticity remains elusive. Thus, the goal of the present study was to use the Ppt1 -/- mouse model (both sexes) to determine whether Ppt1 regulates AMPAR-mediated synaptic transmission and plasticity, which are crucial for the maintenance of homeostatic adaptations in cortical circuits.
Here, we found that basal excitatory transmission in the Ppt1 -/- visual cortex is developmentally regulated and that chemogenetic silencing of the Ppt1 -/- visual cortex excessively enhanced the synaptic expression of GluA1. Furthermore, triggering homeostatic plasticity in Ppt1 -/- primary neurons caused an exaggerated incorporation of GluA1-containing, calcium-permeable AMPARs, which correlated with increased GluA1 palmitoylation. Finally, Ca2+ imaging in awake Ppt1 -/- mice showed visual cortical neurons favor a state of synchronous firing. Collectively, our results elucidate a crucial role for Ppt1 in AMPAR trafficking and show that impeded proteostasis of palmitoylated synaptic proteins drives maladaptive homeostatic plasticity and abnormal recruitment of cortical activity in CLN1.
Access the full article here.
Mechanistic Insights into S-Depalmitolyse Activity of Cln5 Protein Linked to Neurodegeneration and Batten Disease: A QM/MM Study.
Dangat Y, et al. J Am Chem Soc. 2023 Dec 6. Online ahead of print.
ABSTRACT
Ceroid lipofuscinosis neuronal protein 5 (Cln5) is encoded by the CLN5 gene. The genetic variants of this gene are associated with the CLN5 form of Batten disease. Recently, the first crystal structure of Cln5 was reported. Cln5 shows cysteine palmitoyl thioesterase S-depalmitoylation activity, which was explored via fluorescent emission spectroscopy utilizing the fluorescent probe DDP-5. In this work, the mechanism of the reaction between Cln5 and DDP-5 was studied computationally by applying a QM/MM methodology at the ωB97X-D/6-31G(d,p):AMBER level.
The results of our study clearly demonstrate the critical role of the catalytic triad Cys280-His166-Glu183 in S-depalmitoylation activity. This is evidenced through a comparison of the pathways catalyzed by the Cys280-His166-Glu183 triad and those with only Cys280 involved. The computed reaction barriers are in agreement with the catalytic efficiency. The calculated Gibb’s free-energy profile suggests that S-depalmitoylation is a rate-limiting step compared to the preceding S-palmitoylation, with barriers of 26.1 and 25.3 kcal/mol, respectively. The energetics were complemented by monitoring the fluctuations in the electron density distribution through NBO charges and bond strength alterations via local mode stretching force constants during the catalytic pathways. This comprehensive protocol led to a more holistic picture of the reaction mechanism at the atomic level.
It forms the foundation for future studies on the effects of gene mutations on both the S-palmitoylation and S-depalmitoylation steps, providing valuable data for the further development of enzyme replacement therapy, which is currently the only FDA-approved therapy for childhood neurodegenerative diseases, including Batten disease.
Access the full article here.
