Molecular genetics and metabolism最新文献

{"title":"Expanded characterization of glycosylation abnormalities and galactose therapy in a patient with CCDC115-CDG using semi-quantitative N-glycan analysis of total and fractionated plasma glycoproteins, in response to Geerts et al. [1]","authors":"Yupeng Liu , Christina Lam , Sheri Poskanzer , Jenny Thies , Holly Stevens , Wenyue Zhang , Eva Morava , Miao He","doi":"10.1016/j.ymgme.2025.109708","DOIUrl":"10.1016/j.ymgme.2025.109708","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109708"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety profile of idursulfase administered at home in patients with mucopolysaccharidosis II enrolled in the Hunter Outcome Survey","authors":"Barbara K. Burton ,&nbsp;Nathalie Guffon ,&nbsp;Jane Roberts ,&nbsp;Ans T. van der Ploeg ,&nbsp;Simon A. Jones ,&nbsp;Jennifer Audi ,&nbsp;Jaco Botha ,&nbsp;David A.H. Whiteman ,&nbsp;Roberto Giugliani ,&nbsp;Joseph Muenzer","doi":"10.1016/j.ymgme.2026.109734","DOIUrl":"10.1016/j.ymgme.2026.109734","url":null,"abstract":"<div><div>The Hunter Outcome Survey (HOS) collected global, real-world data on the natural history of mucopolysaccharidosis II and its treatment with intravenous idursulfase. For eligible patients, home therapy offers a convenient alternative to in-clinic therapy. Using data in HOS as of January 2023, we provide an updated assessment of the safety/tolerability profile of home therapy with idursulfase. The analysis population comprised 333 patients who had received at least one home infusion and 708 patients who had never received home therapy. Median (10th percentile [P10], 90th percentile [P90]) age at home therapy start was 8.9 (2.9, 21.1) years. Median (P10, P90) ages at latest visit were 15.5 (7.7, 29.3) years in the home therapy group and 13.9 (5.2, 29.0) years in the no home therapy group. Patients received a median (P10, P90) of 6.0 (0.8, 12.0) years of home infusions after 1.8 (0.3, 8.7) years of in-clinic therapy, and these timings varied by geographic region. The infusion-related reaction (IRR) rate was 0.11/patient-year during home therapy, 0.13/patient-year for the in-clinic period for the same patients (first 6 months excluded), and 0.05/patient-year for patients who never received home therapy (first 6 months excluded). More than 60% of IRRs were categorized as mild. The adverse event (AE) rate was lower during home therapy (0.59 AEs/patient-year) than during the in-clinic period for the same patients (0.86 AEs/patient-year). Among patients who never received home therapy, the rate was 0.60 AEs/patient-year. Deaths occurred at a rate of 2.17 deaths/100 patient-years of home therapy and 3.60 deaths/100 patient-years among patients never treated with home therapy. No deaths were deemed related to treatment. The rate of missed infusions was 0.52/year during the home therapy period compared with 1.42/year during the in-clinic period for the same patients and 0.57/year for patients who never received home therapy. Our data indicate a similar safety/tolerability profile for intravenous idursulfase administered at home and in clinic in patients with mucopolysaccharidosis II.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109734"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover 2 / Ed. Board","authors":"","doi":"10.1016/S1096-7192(26)00136-8","DOIUrl":"10.1016/S1096-7192(26)00136-8","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109853"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin therapy to facilitate weight loss in adults with classic maple syrup urine disease","authors":"Ashlin Rodrigues ,&nbsp;Erin Sweigert ,&nbsp;Donna Robinson ,&nbsp;Makenna Kregel ,&nbsp;Joelle Williamson ,&nbsp;Alanna Koehler ,&nbsp;Sean Schreckengast ,&nbsp;Cara Forry ,&nbsp;KaLynn Loeven ,&nbsp;Erik Puffenberger ,&nbsp;Alexis McVey ,&nbsp;Christine Hendrickson ,&nbsp;Andrea Patel ,&nbsp;Anne Thomas ,&nbsp;Sarah Thomas ,&nbsp;Karlla W. Brigatti ,&nbsp;Kevin Strauss ,&nbsp;Grace Loudon Meier","doi":"10.1016/j.ymgme.2026.109730","DOIUrl":"10.1016/j.ymgme.2026.109730","url":null,"abstract":"<div><div>Surplus calories are used to prevent protein catabolism in patients with maple syrup urine disease (MSUD) but can also lead to obesity and its related complications. At present, there are no evidence-based guidelines to inform weight loss strategies for patients with inborn errors of metabolism. Obese MSUD patients often resist weight loss due to the fear of metabolic decompensation, and their dietary options are limited by dependence on medical foods with fixed nutritional composition. We examined the anthropometric and biochemical effects of metformin in nine adults with severe (classic) MSUD who were instructed to reduce their calorie intake from medical food by 10%. Eight participants (67% female) completed the 52-week study; one withdrew following elective liver transplantation. Baseline median age, body mass index (BMI), and glycosylated hemoglobin (HgbA1C) were 33.8 years (IQR 25.3–41.6), 38.3 kg/m² (IQR 31.6–42.2), and 5.3% (IQR 5.0–5.6), respectively. We titrated the daily metformin dose to a median of 2000 mg (IQR 1000–2000) by week 25, at which time seven (88%) participants successfully reduced total calories from medical food by 10%. Metformin was generally well tolerated. Diarrhea was the most common treatment-related complication, affecting 56% of participants, and limited dose escalation in two (22%) of them. No participant achieved the primary outcome of a &gt; 10% BMI change. However, metformin therapy allowed for modest and significant reductions in weight (−2.8%, <em>p</em> = 0.023), BMI (−2.8 kg/m2, <em>p</em> = 0.016), and calories from medical food without altering plasma leucine concentrations or the proportion of dietary protein from intact sources. Serum triglycerides, high-density lipoprotein, and HgbA1C did not change over the study period. Based on these clinical observations, we conclude that classic MSUD patients can safely use metformin to aid weight loss without triggering metabolic instability, and may therefore tolerate more aggressive weight loss strategies.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109730"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SWATH-MS reveals tissue-specific proteomic changes in a Leigh syndrome mouse model","authors":"Sibonelo Glen Khumalo ,&nbsp;Previn Naicker ,&nbsp;Jeremie Zander Lindeque ,&nbsp;Marianne Venter","doi":"10.1016/j.ymgme.2025.109715","DOIUrl":"10.1016/j.ymgme.2025.109715","url":null,"abstract":"<div><div>Mutations in the <em>Ndufs4</em> gene encoding the accessory subunit of complex I (CI) of the mitochondrial oxidative phosphorylation (OXPHOS) system, are the most common causes of Leigh Syndrome (LS). LS is a severe infantile neurodegenerative disorder characterised by various clinical phenotypes ranging from ataxia, cardiomyopathy, swallowing difficulties, visual problems, psychomotor regression to fatal respiratory failure. The mechanistic processes contributing to the onset and progression of these clinical manifestations remain poorly understood.</div><div>This study investigates tissue-specific proteomic changes in a mouse model of LS using quantitative proteomics as a hypothesis-generating technique. Six distinct tissues, namely three brain regions (brainstem, cerebellum, olfactory bulb), heart, kidney, and liver, were collected from the LS mouse model (<em>Ndufs4</em> KO mice) and compared to wild type (WT) controls using SWATH-MS analysis as a data acquisition method. Functional enrichment analysis revealed distinct tissue-specific cellular responses which include a shift toward amino acid metabolism in the heart, increased mitochondrial translation in the kidney, and alterations in phase II detoxification pathways in the liver. Our results unravel candidate mechanisms for tissue-specific vulnerability and highlight the regulation of PTEN gene transcription as potential driver of neurodegeneration. These findings provide data-driven hypotheses for tissue-specific vulnerability in LS, highlighting potential mechanisms and therapeutic targets.</div><div>This study established a foundation for future hypothesis-driven research into the tissue-specific pathophysiology of mitochondrial disease.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109715"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the clinical, neuroimaging, and genetic spectrum of PLPBP deficiency: multicenter case series and systematic review","authors":"Hanin Alsini ,&nbsp;Ali Al-Otaibi ,&nbsp;Imran Ali Khan ,&nbsp;Khalid Hundallah ,&nbsp;Brahim Tabarki ,&nbsp;Majid Alfadhel","doi":"10.1016/j.ymgme.2026.109764","DOIUrl":"10.1016/j.ymgme.2026.109764","url":null,"abstract":"<div><h3>Objective</h3><div>To describe the phenotype, genotype, neuroimaging features, and outcome of <em>PLPBP</em>-related vitamin B₆-dependent epilepsies. We present a systematic review, along with a multicenter case series of patients with <em>PLPBP</em> deficiency.</div></div><div><h3>Methods</h3><div>We collected individual data on clinical, radiological, genetic, and outcomes for a multicenter case series (<em>n</em> = 8) and all previously published cases (<em>n</em> = 46). We conducted a thematic analysis to identify consistent features across all cases and applied a clinical score system specifically developed to assess the impact of <em>PLPBP</em>-related vitamin B₆-dependent epilepsy on neurodevelopmental and seizure outcome in each case.</div></div><div><h3>Results</h3><div>We identified 14 eligible studies involving 46 patients. Including our additional cases, the total number of individuals with <em>PLPBP</em> variants increased to 54. The most common type of variant was missense variants (48%), with the variant c.370–373del being the most frequently reported (18.5%). Based on our clinical severity scoring system, which evaluates the degree of neurodevelopmental impairment and seizure control, more than two thirds of patients were classified as having moderate to severe disease. All individuals in the reviewed studies presented with early neonatal seizures, with the majority occurring within the first 24 h of life (55.5%) or the first week of life (76%). Common clinical features observed included antenatal anomalies, prematurity, fetal distress, and microcephaly. Analysis of brain MRI studies identified anomalies in 65% of cases, including white matter abnormalities (54%), periventricular or temporal cysts (27%), anomalies of the corpus callosum (15.4%), and global brain underdevelopment with broad gyri and shallow sulci (44%). Genotype-phenotype analysis revealed an association of missense variants and compound heterozygous variants with an attenuated phenotype, while biallelic truncating variants and homozygous variants were linked to severe phenotypes and/or early mortality.</div></div><div><h3>Conclusions</h3><div>This systematic review and multicenter case series of a large cohort of individuals with <em>PLPBP</em> deficiency delineates the clinical, radiological, and genetic spectrum of <em>PLPBP</em>-related vitamin B₆-related epilepsies, an autosomal-recessive disease. It also highlights the best treatment approaches and potential predictors for disease severity and survival.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109764"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhabdomyolysis due to mtDNA pathogenic variants: Report of a subject with a novel MT-CO3 variant and review of the literature","authors":"Emanuele Barca ,&nbsp;Nuri Jacoby ,&nbsp;Ali Naini ,&nbsp;Michael L. Miller ,&nbsp;Valentina Emmanuele ,&nbsp;Christopher J. Winfree ,&nbsp;Saba Tadesse ,&nbsp;Kurenai Tanji ,&nbsp;Michio Hirano","doi":"10.1016/j.ymgme.2026.109767","DOIUrl":"10.1016/j.ymgme.2026.109767","url":null,"abstract":"<div><div>Rhabdomyolysis can be due to mitochondrial myopathy, but mitochondrial DNA (mtDNA) pathogenic variants are often overlooked in standard genetic panels. We report a 41-year-old woman with recurrent rhabdomyolysis due to a novel <em>MT-CO3</em> variant. Muscle biopsy showed cytochrome <em>c</em> oxidase-negative fibers that segregated with high heteroplasmic load on single-fiber. We additionally review previously reported mtDNA variants associated with rhabdomyolysis, highlighting the diagnostic relevance of mtDNA analysis and tissue-specific testing in unexplained rhabdomyolysis.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109767"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole genome sequencing from dried blood spots for newborn screening of Menkes disease and 36 other actionable inherited neurometabolic disorders","authors":"Stephen G. Kaler ,&nbsp;Lalitha Venkataraman ,&nbsp;Minh T. Pham ,&nbsp;Benjamin J. Kennedy ,&nbsp;Mohammad Marhabaie ,&nbsp;Daniel C. Koboldt","doi":"10.1016/j.ymgme.2026.109763","DOIUrl":"10.1016/j.ymgme.2026.109763","url":null,"abstract":"<div><div>Tandem mass spectrometry is currently used by the Ohio Department of Health to screen newborn infants for 36 medically actionable inborn errors of metabolism. As a complementary test for infants with abnormal biochemical screens, whole genome sequencing (WGS) theoretically could reduce false-positive results, facilitate timely case resolution and, in some instances, indicate a more specific diagnosis than obtained initially. Menkes disease is a X-linked recessive disorder of human copper metabolism with a predicted minimum birth prevalence of 1 in 34,810 live male births. Recent progress in treatment options for Menkes heighten the importance of newborn screening (NBS) to identify this illness within the window of therapeutic opportunity, the first 4 to 6 weeks of life. We developed a DNA extraction protocol from dried blood spots that yielded high quality DNA for whole genome sequencing and studied 24 subjects with known <em>ATP7A</em> variants. Analysis was confined to genes (<em>n</em> = 55) for neurometabolic conditions currently screened for in Ohio (<em>n</em> = 36) plus <em>ATP7A</em> (Menkes disease). WGS detected all <em>ATP7A</em> variants including 7 missense, 5 splice site, 4 copy number variants, 4 nonsense, 3 indels, and 1 missense/splice site. WGS also detected 5 heterozygous pathogenic variants in 5 genes that encode conditions for which Ohio screens. Our results confirm the feasibility and reliability of this approach for early Menkes disease detection and to complement tandem mass spectroscopy for detection of other actionable inherited disorders.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109763"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis, treatment, and follow-up of Fabry disease in pediatrics","authors":"Juan Guillermo Cárdenas-Aguilera ,&nbsp;Kelly Rocío Chacón-Acevedo ,&nbsp;Ana María Zarante-Bahamón ,&nbsp;Ana Katherina Serrano-Gayubo ,&nbsp;Juan Carlos Prieto-Rivera ,&nbsp;Adriana Isabel Meza-Martínez ,&nbsp;Jorge Armando Rojas-Martínez ,&nbsp;Jimena Adriana Cáceres-Mosquera ,&nbsp;Maryuri Liseth Duarte-Amorocho ,&nbsp;Claudia Milena Pérez-Alfonso ,&nbsp;Clímaco Andrés Jiménez-Triana ,&nbsp;Richard Baquero-Rodríguez ,&nbsp;Claudia Ximena Flórez-Rodríguez ,&nbsp;María Fernanda Reina-Ávila ,&nbsp;Gustavo Adolfo Guerrero-Tinoco ,&nbsp;Pilar Guarnizo-Zuccardi ,&nbsp;Jazmín Sánchez-Gómez ,&nbsp;Catalina Vélez-Echeverry ,&nbsp;Liliana María Rubio-Elorza ,&nbsp;Paola del Roció Mera-Solarte ,&nbsp;Fernando Javier Perretta","doi":"10.1016/j.ymgme.2025.109709","DOIUrl":"10.1016/j.ymgme.2025.109709","url":null,"abstract":"<div><h3>Introduction</h3><div>Fabry disease (FD), also known as Anderson-Fabry disease, is a heterogeneous, multisystem lysosomal storage disorder with an X-linked inheritance pattern. Its estimated prevalence in the general population ranges from approximately 1 in 40,000 to 1 in 100,000 individuals.</div><div>FD results from partial or complete deficiency of the lysosomal enzyme alpha-galactosidase A (α-Gal A), caused by pathogenic variants in the <em>GLA</em> gene. This enzymatic deficiency leads to progressive lysosomal accumulation of glycosphingolipids, resulting in multisystem involvement with a broad clinical spectrum. Clinical manifestations may appear as early as childhood.</div></div><div><h3>Objective</h3><div>To develop evidence-based recommendations for the diagnosis, treatment, and follow-up of pediatric patients with FD.</div></div><div><h3>Materials and Methods</h3><div>A literature search was conducted in Medline and Embase for studies published between January 2021 and May 2025. Additional information was obtained from development group websites, consensus documents, technology evaluations, Google Scholar, clinical experts, and reference lists. The quality of evidence was assessed according to the type of source. A modified Delphi consensus process was carried out with external experts, and an 80 % agreement threshold was established to define the final recommendations.</div></div><div><h3>Results</h3><div>The evidence search identified 47 publications. Consensus was reached on 57 recommendations regarding diagnosis, treatment, and surveillance. These recommendations were validated by external clinical experts from Colombia, Argentina, Spain, Mexico, and the USA.</div></div><div><h3>Conclusions</h3><div>The recommendations presented in this document are based on the most up-to-date evidence available at the time of the search and the judgment of clinical experts. They are expected to support daily clinical practice for the diagnosis, treatment, and follow-up of pediatric patients with FD.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109709"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzyme replacement therapy for CLN1 batten disease that crosses the blood-brain-barrier","authors":"Renuka Raman ,&nbsp;Ben Horst ,&nbsp;Zahra Shahrokh ,&nbsp;Nader Hatambeygi ,&nbsp;Maryam Zare ,&nbsp;Magdalena Leszczyniecka ,&nbsp;Joshua S. Harris ,&nbsp;William A. Banks ,&nbsp;Kim M. Hansen ,&nbsp;Michelle A. Erickson ,&nbsp;Sean Ekins","doi":"10.1016/j.ymgme.2026.109733","DOIUrl":"10.1016/j.ymgme.2026.109733","url":null,"abstract":"<div><div>CLN1 Batten disease is caused by mutations in the CLN1 gene which codes for the lysosomal enzyme palmitoyl-protein thioesterase-1 (PPT1). Disease progression is marked by intellectual and motor deterioration, seizures, vision loss, and early mortality. There are no approved treatments for this severe pediatric condition. We describe the development and characterization of recombinant human PPT1 (rhPPT1) suitable for use as a clinical enzyme replacement therapy in CLN1 Batten patients. rhPPT1 displays similar mannose-6-phosphate receptor (M6PR)-dependent uptake kinetics in neuronal cell lines from human, rat and non-human primate but not in mouse cells. rhPPT1 crosses the blood-brain-barrier (BBB) in adult mice which is uncommon for unmodified lysosomal enzymes, and is independent of the M6PR and sialic acid receptors even though analytical characterization of rhPPT1 shows complex M6P and sialic acid containing glycans. Our findings suggest for the first time that intravenous dosing of rhPPT1 may be complementary to other dosing strategies in CLN1 patients and may expand its use for other applications.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"147 3","pages":"Article 109733"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}