ribitol (BBP-418) / BridgeBio - LARVOL DELTA

Urinary metabolomics profile in children with ureteropelvic junction obstruction. (PubMed, Metabolomics) - "Despite the limited size and age spanning of the cohort evaluated here, the statistical quality of the present study, that certified 17 metabolites by both univariate and multivariate methods among 94 discriminant metabolites, deriving from NOHN, OHN, and CTR group comparisons, may contribute to pave the way into searching valuable biomarkers for the obstructive HN setting up and progression."

Biomarker • Journal • Nephrology • Renal Disease

One-pot enzymatic synthesis of the sugar nucleotide CDP-ribitol. (PubMed, RSC Chem Biol) - "Here, we demonstrate the one-pot enzymatic synthesis of CDP-ribitol from the readily available precursor ribitol. We also explore the synthesis of bioorthogonally tagged derivatives and other CDP conjugates, thereby providing valuable new tools for glycoscience research."

Journal

Fortify: Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I) (clinicaltrials.gov) - P3 | N=112 | Active, not recruiting | Sponsor: ML Bio Solutions, Inc. | N=81 ➔ 112

Enrollment change • Muscular Dystrophy

Comparative metabolomic profiling reveals salinity tolerance mechanisms in a rice introgression line. (PubMed, Metabolomics) - "Comparative analysis identified differentially accumulated metabolites (DAMs) spanning diverse chemical classes, including amino acids, sugars and carbohydrates, lipids, organic acids, cofactors, electron carriers, and nucleotides. Under salt stress (SS), 201 DAMs (89 upregulated and 112 downregulated) were detected in JN relative to JU. Notably, metabolites such as allantoin, glycitin, nicotinamide ribotide, D-arabinono-1,4-lactone, violanthin, L-methionine S-oxide, ribitol, lysine, rutin, glutamine, pantothenic acid, and quinic acid, showed significant differential accumulation. Pathway enrichment analysis revealed significant enrichment of arginine biosynthesis, purine metabolism, and alanine, aspartate, and glutamate metabolism, indicating extensive reprogramming of nitrogen and energy-associated metabolic pathways under salinity stress. Integration of transcriptomic and metabolomic datasets from the SS experiments further identified ten differentially expressed..."

Clinical • Journal

High-Throughput Analysis Reveals Stable Metabolome of Paxillus involutus Under White Light Exposure Despite Reduced Mycelium Growth. (PubMed, Int J Mol Sci) - "Lyxose and ribitol showed significant differences between treatments based on unadjusted p-values, as confirmed by individual t-tests, whereas only xylonic acid remained significant after FDR correction (α = 0.05)...This first high-throughput metabolomic analysis of ectomycorrhizal mycelium exposed to light indicates that, although light is commonly considered a stress factor for soil fungi, it does not cause significant modifications in the Paxillus involutus metabolome, despite visible phenotypic changes in the mycelium. Although this study focuses solely on mycelium and does not investigate different light spectra, it may help explain potential implications for symbiotic plant interactions under fluctuating light conditions in soil ecosystems."

Journal

Synthetic studies toward the total synthesis of zwitterionic polysaccharides (ACS-Fall 2026) - "This unit, composed of a 1,5-bisphosphorylated ribitol, ribitol, and the rare bacterial sugar AAT, represents the first known bisphosphorylated moiety found in ZPSs. Our synthetic strategy, centered on controlled stereoselective assembly through the exploitation of solvent and electronic effects, enables the expedient construction of this trisaccharide core."

Infectious Disease

Phosphonomethyl (Thio)Phosphonamidite Reagents for the Construction of Phosphonylmethyl Phosphono(Di)Thioate Mono- and Diesters. (PubMed, Chemistry) - "Immediate global deprotection or subsequent site-selective deprotection of the terminal phosphonate followed by a phosphonodiester condensation furnishes unprecedented phosphonylmethyl phosphono(di)thioate mono- and nonsymmetrical diesters, respectively. Using this method, we have assembled four nucleoside diphosphate analogs as well as a set of eight stable CDP-glycerol and CDP-ribitol mimics, all in multimilligram amounts."

Journal

Safety, Tolerability, Pharmacokinetics, Food Effect of Ribitol, and Its Effect on QTcF in Healthy Adults: First-in-Human, Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Studies. (PubMed, Clin Pharmacol Drug Dev) - "Assay sensitivity was demonstrated with the expected effect of moxifloxacin. These results support further development of ribitol for the treatment of LGMDR9."

Clinical • First-in-human • Journal • P1 data • PK/PD data • Addiction (Opioid and Alcohol) • Genetic Disorders • Muscular Dystrophy • FKRP

An integrated lifestyle-, genetic- and metabolomics-based prediction model for mild cognitive aging in the HCHS/SOL. (PubMed, NPJ Dement) - "Diabetes and the metabolite ribitol had the highest influence on prediction of MCI. Although prediction performance was not especially high and did not vary greatly across models, incorporating information on diabetes, ancestry and metabolites may help improve prediction of GCSC and MCI."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Diabetes • Metabolic Disorders • APOE

Expanding the Phenotypic Spectrum of FKTN Mutations: A Case of Generalized Epilepsy, Neurodevelopmental Delay, andHyperCKemia (ICNMD 2026) - "Background: The FKTN gene (9q34.1) encodes fukutin, a ribitol-5-phosphate transferase essentialfor the functional - glycosylation of alpha-dystroglycan...He started therapy with Levetiracetam (250 mg BID) was initiated, achieving seizure control...While brain MRI was unremarkable, the EMG performed on the right deltoid suggested a myogenic process with low-amplitude, polyphasic motor unit potentials... This case suggests that the phenotypic spectrum of FKTN mutations may include generalized epilepsy even in the presence of paucisymptomatic muscle involvement."

Clinical • Neurodevelopmental • Cardiomyopathy • Cardiovascular • CNS Disorders • Developmental Disorders • Epilepsy • Heart Failure • Muscular Dystrophy • FKRP

Interim Analysis from Ongoing Phase 3 FORTIFY Study of BBP-418 for LGMD2I/R9 Meets Efficacy Endpoints (ICNMD 2026) - P3 | "The interim analysis results from the ongoing 3-year FORTIFY Phase 3 trial demonstrated that BBP-418 provides significant improvements in αDG glycosylation, decreases in CK levels and functional benefits with a favorable safety profile. These data support BBP-418 as the potential first disease-modifying therapy for LGMD2I/R9."

Clinical • P3 data • P3 data: top line • Muscular Dystrophy

Open-Label Extension Study of BBP-418 (Ribitol) for LGMD2I/R9 (clinicaltrials.gov) - P3 | N=107 | Active, not recruiting | Sponsor: ML Bio Solutions, Inc.

New P3 trial • Muscular Dystrophy

Examining the physiological and molecular impact of biochar on polyol synthesis and drought resistance in tomato plants. (PubMed, Sci Rep) - "Here we integrate physiological (polyol pools, SDH enzyme) and molecular (SDH transcripts) readouts with explicit soil and material characterisation to test how a wood-derived biochar alters the sorbitol/ribitol-SDH axis during water limitation...Novelty: The data indicate that biochar attenuates the polyol-associated stress response (lower osmolyte demand and SDH induction) while maintaining growth, consistent with improved plant water status. These findings suggest that biochar may contribute to reducing osmotic stress responses, complementing its agronomic benefits in arid systems and supporting sustainable tomato production."

Journal

Differential rumen and hindgut microbiome and metabolome in Holstein female calves with divergent feed efficiency. (PubMed, Microbiome) - "In summary, this multi-omics study reveals that high feed efficiency in calves is associated with distinct microbial ecosystems characterized by functions such as starch degradation and propionate production, where glutamate metabolism serves as a central node. Video Abstract."

Journal • Gastrointestinal Disorder

Chemical Probes to Reveal the Assembly and Dynamics of Wall Teichoic Acids. (PubMed, J Am Chem Soc) - "Here, we introduce azido-ribitol (RibAz) derivatives that enter the WTA biosynthetic pathway in Staphylococcus aureus via a salvage-like mechanism and incorporate into the poly(ribitol phosphate) backbone...RibAz probes provide a generalized chemical approach for interrogating WTA function, abundance, and dynamics, and establish a foundation for mechanistic studies of cell wall biogenesis. Such data can inform antibiotic discovery efforts to combat antimicrobial resistance."

Journal • Infectious Disease

MLB-01-007: Long-Term Effects of BBP-418 (Ribitol) in Participants with LGMD2I/R9 (clinicaltrialsregister.eu) - P2/3 | N=31 | Not yet recruiting | Sponsor: ML Bio Solutions Inc.

New P2/3 trial • Muscular Dystrophy

Clinical presentations and pathophysiological mechanisms of dystroglycanopathy: advancing therapeutic strategies. (PubMed, Lancet Neurol) - "Advances in the understanding of the pathophysiology and genetics have identified new therapeutic targets. Emerging therapeutic approaches, including adeno-associated virus gene therapy for limb-girdle muscular dystrophy associated with pathogenic variants in FKRP (the most common form of dystroglycanopathy) and ribitol-based therapies, are being evaluated in clinical trials and could expand treatment options."

Journal • Review • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Mental Retardation • Muscular Dystrophy

BridgeBio Announces FDA Acceptance and Priority Review of NDA for BBP-418 for LGMD2I/R9 (The Manila Times) - "The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of November 27, 2026, and BridgeBio is poised to launch BBP-418 upon approval. The FDA also notified the Company that it is not currently planning to hold an advisory committee meeting to discuss the application....In the Phase 3 FORTIFY trial, BBP-418 met all primary and secondary endpoints at the pre-specified 12-month interim analysis, showing treated individuals improving while placebo recipients declined across every key measure."

FDA event • FDA filing • PDUFA • Priority review • Muscular Dystrophy

Rational engineering of ribitol dehydrogenase for enhanced thermostability and efficient biocatalytic production of allitol. (PubMed, J Sci Food Agric) - "This study significantly improved the thermostability of RDH using consensus-guided interfacial design and constructed a cofactor-regenerating enzyme complex for the efficient biocatalytic production of allitol."

Journal

Single AAV vector base editing improves dystrophic phenotype in L276I FKRP-mutant mouse models of dystroglycanopathy (ASGCT 2026) - "Currently, no treatment is available, although experimental therapies such as AAV-mediated FKRP gene expression and ribitol treatment are being tested clinically...Additionally, improved skeletal muscle pathology was demonstrated by a decrease in the percentage of central nucleated fibers, as well as reduced proportion of smaller fibers in size distribution in TA muscle. Conclusion Our findings advance the therapeutic potential of base editing to achieve enhanced function of the target protein by alteration of point mutation to non-WT variants, thus greatly widening the scope of this strategy for treating genetic and non-genetic diseases."

Preclinical • CNS Disorders • Fibrosis • Genetic Disorders • Immunology • Muscular Dystrophy • Respiratory Diseases • FKRP

Improvements in dystrophic pathology of P448L-FKRP mutant mouse model following overexpression of FGGY and AKR1B1 (ASGCT 2026) - "We recently reported that several pentoses, specifically ribitol, ribose and ribulose are all able to enhance matriglycan synthesis. Combinatorial tests of the pentoses with overexpression of these genes are ongoing and the result could provide further clues for enhancing matriglycan expression as more effective treatment for dystroglycanopathies."

Preclinical • Gene Therapies • Muscular Dystrophy • AKR1B1 • FKRP

Poikilohydria, polyols, and homeoviscosity: lichen metabolomic remodeling across environmental gradients. (PubMed, Front Plant Sci) - "The metabolome was primarily centered on polyols: arabitol was the predominant metabolite (49.9% of total relative abundance), followed by ribitol, sucrose, sorbitol, and mannitol...This and other differential pathways indicated coupled adjustments in carbon handling and stress physiology. This is the first continent-scale characterization of low-molecular-weight metabolomic variation in a lichen, revealing environmentally linked metabolic remodeling beyond the traditionally studied secondary metabolites and defining new chemoenvironmental markers as the metabolic basis of poikilohydric resilience in lichens."

Journal • Metabolic Disorders

Carbohydrate conversion and microbial community restructuring following Saccharomyces cerevisiae inoculation during Pu-erh tea fermentation. (PubMed, Int J Food Microbiol) - "Compared with naturally fermented controls, yeast-inoculated teas exhibited a marked decrease in cell-wall cellulose, concomitant increases in hemicellulose-, pectin- and lignin-derived fragments, and significantly elevated levels of glucose, fructose, galactose, trehalose, ribitol and arabitol...This enzyme ensemble accelerates depolymerization of β-1,4-glucan and α-1,6-glycosidic linkages in cellulose and pectin side chains, liberating neutral sugars and polyols that chemically account for the enhanced sweetness, thickness and smooth mouthfeel of inoculated teas. We propose a yeast-driven polysaccharide-monosaccharide conversion mechanism that provides a molecular basis for carbohydrate transformation in Pu-erh tea and offers a general framework for modulating carbohydrate-derived flavor attributes in fermented plant-based foods."

Journal • HK1

Crystal structures of Klebsiella oxytoca ribitol dehydrogenase in complex with NAD+, d-allose, or d-allulose reveal insight into substrate recognition. (PubMed, FEBS Lett) - "Impact statement This research reveals an insight into a substrate recognition mechanism in the flexible region of ribitol dehydrogenase. Because ribitol dehydrogenase is a member of the short-chain reductases/oxidases (SDR) family, the current study will provide further insight into related enzymes that harbor the flexible region."

Journal

Plasma Metabolites, Blood-borne Microvesicles and History of Preeclampsia as predictors of Coronary Artery Calcification in Postmenopausal Women. (PubMed, Am J Physiol Heart Circ Physiol) - " Patients with, versus those without, CAC demonstrated i) less favorable cardiovascular and metabolic profiles; ii) elevation in six EVs populations, including those positive for TF (tissue factor), CD3 (T-cells), SM22α (smooth muscle cells), Pref-1 (adipocytes), FABP4 (adipocytes/macrophages) and p16 (senescent cells); iii) significantly higher levels of proline, allothreonine (amino acid metabolism) and ribitol (carbohydrate metabolism), and lower levels of lactic acid (carbohydrate metabolism); and iv) significantly increased risk of developing CVD and chronic kidney disease (CKD) (P<0.05 for all). In the CAC positive group, women with PE vs those with normotensive pregnancy histories, demonstrated 4-times higher risk of developing cardiovascular events or CKD later in life (P=0.028). Selected plasma metabolites, EVs and PE history could serve as biomarkers of and potential therapeutic targets for CAC and CVD in postmenopausal women."

Journal • Cardiovascular • Chronic Kidney Disease • Gynecology • Nephrology • Renal Disease • Women's Health • FABP4