ribitol (BBP-418) / BridgeBio - LARVOL DELTA

Design and Evaluation of FKRP Dimer Expression for Restoration of Functional Matriglycan in a LGMD 2I/R9 Mouse Model (ASGCT 2025) - "Of these, Limb Girdle Muscular Dystrophy 2I/R9 results from mutation-bearing Fukutin-related protein (FKRP) having little or no functional capacity as ribitol-phosphate (RboP) transferase to elongate the core M3 glycan (matriglycan) which is required to bind laminin and other proteins, securing the muscle membrane and extracellular matrix...This novel approach to FKRP gene replacement has the potential to restore greater levels of matriglycan expression at lower doses of AAV thereby reducing dose related toxicity. Disease Focus of Abstract:Muscular Dystrophy (all forms)"

Preclinical • Fibrosis • Immunology • Inflammation • Muscular Dystrophy • FKRP

Targeting of ribitol metabolic pathway using AAV to enhance glycosylation and therapeutic efficacy of metabolites in the FKRP-P448L mutant mouse. (ASGCT 2025) - "By targeting the biosynthetic pathway of ribitol-5-phosphate the effectiveness of ribitol treatment can potentially be improved for treating FKRP-related muscular dystrophies. Disease Focus of Abstract:Muscular Dystrophy (all forms)"

Preclinical • Muscular Dystrophy • AKR1B1 • FKRP

Meniscomyces senecionis sp. nov., a novel anamorphic basidiomycete yeast species. (PubMed, Int J Syst Evol Microbiol) - "The novel strain also exhibits distinct physiological traits, including an inability to assimilate maltose and cellobiose and the ability to utilize d-xylose, d-ribose, glycerol, ribitol, d-mannitol, dl-lactate and d-gluconate...nov. (Holotype: CICC 33585; MycoBank: MB 857392) is proposed."

Journal

ELUCIDATING THE ROLE AND MECHANISM OF TUFM IN LGR5 ACTIVATION WITHIN WNT SIGNALING IN NEUROGENIC TUMOR CELLS AND ENHANCING OF NEURAL STEM CELLS USING TUFM (ADPD 2025) - "Through proteomics analysis, common changes in protoporphyrinogen oxidase (PPO), suppressor APC domain - containing protein 2 (SAPCD2), katanin p60 ATPase -containing subunit A -like 2 (KATNAL2), Rab GTPase - binding effector protein 2 (RABEP2), ribitol -5-phosphate xylosyltransferase 1 (RXYLT1), and organic solute carrier partner 1 (OSCP1) were observed in the two cell types under TUFM regulation... The cellular activities of genes and proteins associated with the TUFM, Lgr5, and Wnt signaling pathway were validated in SH -SY5Y cells and hNSCs. Based on our previous research findings, we have confirmed that substantial involvement of splicing and mRNA transcription among various mechanisms. Modulating splicing factors triggers the activation of TUFM and Lgr5 within the Wnt signaling pathway, consequently enhancing the functionality of hNSCs."

Tumor cell • Brain Cancer • CNS Disorders • Oncology • PPOX • SAPCD2 • SPON1 • TUFM

Synergistic Effect of Ribitol and Shikonin Promotes Apoptosis in Breast Cancer Cells. (PubMed, Int J Mol Sci) - "Metabolomic analysis supports the premise that inhibition of the Warburg effect is involved in shikonin-induced cell death, which is likely further enhanced by dysregulation of glycolysis and the tricarboxylic acid (TCA) cycle, afflicted by ribitol treatment. In conclusion, the present study demonstrates that the metabolite ribitol selectively enhances the cytotoxic effect mediated by shikonin against breast cancer in vitro."

Journal • Breast Cancer • Oncology • Solid Tumor • BCL2L1 • MCL1 • MYC

Substrate flexibility of Mycoplasma fermentans mf1 phosphorylcholine transferase. (PubMed, Glycoconj J) - "Mf1 activity is inhibited by β-glycerophosphate, an isomer of part of CDP-glycerol which is known to compete with CDP-ribitol in enzymatic reactions catalyzed by fukutin, a human protein sharing structural homology with mf1. For the first time, a phosphorylcholine transferase, mf1, could be biochemically characterized in vitro and its lipid products with zwitterionic phosphodiesters attached could be detected specifically with the pentraxin serum amyloid P."

Journal

Unraveling the genome of Proteus mirabilis strain representing the O78 serogroup: Insights into the unique features of the O-antigen biosynthesis gene cluster. (PubMed, Infect Genet Evol) - "The function of licD in this strain appears to be linked to the ispD gene, potentially involved in the biosynthesis of CDP-ribitol. Additionally, we explored other genomic features, including the strain's genetic similarity to closely related microorganisms, the presence of antimicrobial resistance genes, and prophage elements. This study provides valuable insights into the genetic factors underlying the pathogenicity of the P. mirabilis 1B-m strain and its potential implications for hospital-acquired infections."

Journal • Infectious Disease • Inflammation

BridgeBio Pharma Reports Fourth Quarter and Full Year 2024 Financial Results and Commercial Update (GlobeNewswire) - "FORTIFY, the Phase 3 clinical trial of BBP-418 in LGMD2I/R9...The Company expects to achieve last participant – last visit and report topline results of the interim analysis cohort in the second half of 2025...CALIBRATE, the Phase 3 clinical trial of encaleret in ADH1...The Company expects to achieve last participant – last visit and report topline results in the second half of 2025...PROPEL 3, the Phase 3 clinical trial of infigratinib in achondroplasia, the most common form of disproportionate short stature, is fully enrolled with 114 participants randomized. The Company expects to achieve last participant – last visit in the second half of 2025."

P3 data: top line • Trial status • Endocrine Disorders • Hypoparathyroidism • Muscular Dystrophy • Rare Diseases

Expression and biochemical characterization of a novel NAD+-dependent xylitol dehydrogenase from the plant endophytic fungus Trichoderma gamsii. (PubMed, Protein Expr Purif) - "The Km values for xylitol, ribitol, and d-sorbitol were 5.23 ± 0.68 mM, 8.01 ± 1.22 mM, and 12.34 ± 1.37 mM, respectively. Collectively, the results will contribute to understanding the biochemical properties of a novel XDH from the filamentous fungi and provide a promising XDH for industrial production of ethanol."

Journal • Addiction (Opioid and Alcohol)

A novel polysaccharide in the envelope of S. aureus influences the septal secretion of preproteins with a YSIRK/GXXS motif. (PubMed, J Bacteriol) - "Both Staphylococcus aureus and Bacillus subtilis elaborate WTAs made of poly-glycerol or poly-ribitol phosphates...Here, we find that this polymer could help define the composition of the septal compartment, the site of cell division also used to recruit preproteins with a YSIRK/GXXS motif. Thus, the envelope of S. aureus may be more complex than previously thought with minor wall polymers contributing some discrete functions."

Journal • Infectious Disease

Wall teichoic acid glycosylation of bovine-associated Staphylococcus aureus strains. (PubMed, Vet Microbiol) - "WTA consist of polymerized ribitol-phosphate backbone that is modified with N-acetylglucosamine (GlcNAc) moieties in different configurations by the glycosyltransferases TarS (β-1,4-GlcNAc), TarM (α-1,4-GlcNAc) and TarP (β-1,3-GlcNAc)...Interestingly, a divergent tarM allele was present in strains of clonal complexes (CC) 49 and the mastitis-associated CC151, but its function was similar to canonical tarM. In conclusion, we demonstrated that bovine-associated S. aureus strains show similar variation in WTA GlcNAc decoration as human S. aureus strains, despite the presence of a divergent tarM allele."

Journal

Causal Association Between Cerebrospinal Fluid Metabolites and Parkinson's Disease: A Two-Sample Bidirectional Mendelian Randomization Study. (PubMed, Behav Brain Res) - "The identified CSF metabolites may serve as potential CSF metabolic biomarkers for screening and preventing PD in clinical practice and could also be considered as candidate molecules for future mechanistic exploration and drug target selection."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Ribitol and ribose treatments differentially affect metabolism of muscle tissue in FKRP mutant mice. (PubMed, Sci Rep) - "Ribose treatment significantly increases level of ribonate and elevates levels of advanced glycation end products. Further analysis is required to determine which metabolite is prudent to use for long-term daily treatment of dystroglycanopathies."

Journal • Preclinical • Gene Therapies • FKRP

Aldolase B Deficient Mice Are Characterized by Hepatic Nucleotide Sugar Abnormalities. (PubMed, J Inherit Metab Dis) - "Of interest, multiple other hepatic nucleotide sugars not involved in N-linked glycosylation, such as hepatic UDP-glucuronic acid, UDP-xylose, CMP-N-acetyl-beta-neuraminic acid, and CDP-ribitol (p = 0.002, p = 0.003, p = 0.002, p = 0.002), were found to have altered levels as well...Future studies are needed to identify the underlying mechanisms responsible for the abnormal hepatic nucleotide sugar pattern and intrahepatic lipid accumulation in HFI. Trial Registration: PCT ID: PCTE0000340, this animal experiment is registered at (https://preclinicaltrials.eu/)."

Journal • Preclinical • Genetic Disorders

H2-driven xylitol production in Cupriavidus necator H16. (PubMed, Microb Cell Fact) - "This study highlights the efficient utilization of renewable hydrogen as a reducing agent to power cofactor recycling. Hydrogen-oxidizing bacteria, such as C. necator, can be promising hosts for performing hydrogen-driven biocatalysis."

Journal

Metabolomic profiles of infants classified as sudden infant death syndrome: a case-control analysis. (PubMed, EBioMedicine) - "We identified metabolite biomarkers within key biological pathways and processes (e.g., nitrogen metabolism, lipid and fatty acid metabolism, stress response, nerve cell communication, hormone regulation, oxidative stress) with potential implications in SIDS pathology. Further research is needed to validate these biomarkers in additional SIDS cohorts."

Journal • Developmental Disorders • Otorhinolaryngology • Preventive care

Genetic determinants of cerebrospinal fluid metabolites and risk of Guillain-Barré syndrome: A bidirectional two-sample Mendelian randomization study. (PubMed, Medicine (Baltimore)) - "In the forward MR analysis, we identified a causal relationship between 15 CSF metabolites, including ribitol levels (odds ratio = 3.833, 95% confidence interval: 1.949-7.540, P = 9.87E-05), and the risk of developing GBS...Our findings suggest that the identified CSF metabolites and metabolic pathways can serve as valuable biomarkers for clinical screening and prevention of GBS. They may also be considered as candidate molecules for future research into the underlying mechanisms and for selecting drug targets."

Biomarker • Journal

Advances in the biosynthesis of D-allulose. (PubMed, World J Microbiol Biotechnol) - "Enzymatic catalysis for the conversion of starch or glycerol to D-allulose is performed mainly by enzymes such as isoamylase (IA), glucose isomerase (GI), D-allulose 3-epimerase (DPE), D-allulose-6-phosphate 3-epimerase (A6PE), D-allulose 6-phosphate phosphatase (A6PP), ribitol 2-dehydrogenase (RDH), glycerophosphate kinase (GK), glycerophosphate oxidase (GPO), and dihydroxyacetone phosphate (DHAP)-dependent aldolase...It has thus become the main method for producing D-allulose. This article reviews the progress in research on the biosynthetic production of D-allulose, focusing on the enzymes involved and their enzymatic properties, and discusses the production prospects for D-allulose."

Journal • Review • Diabetes • Genetic Disorders • Obesity

Bioactive Potential of the Sulfated Exopolysaccharides From the Brown Microalga Halamphora sp.: Antioxidant, Antimicrobial, and Antiapoptotic Profiles. (PubMed, Anal Sci Adv) - "Gas chromatography-mass spectrometry analysis revealed that the carbohydrate fraction consisted of xylose, l-galactose, d-galactose, glucose, ribitol, mannose, and inositol with corresponding mole percentages of 40.55, 13.25, 13.00, 9.95, 9.82, 2.90, and 2.28, respectively...Overall, the findings of this study suggest the possibility of using the EPS extract of Halamphora sp. as an additive for nutraceutical and cosmetic purposes."

Journal • CASP3 • CASP9

Diethyl aminoethyl hexanoate reprogramed accumulations of organic metabolites associated with water balance and metabolic homeostasis in white clover under drought stress. (PubMed, Front Plant Sci) - "In response to drought stress, the DA-6 induced accumulations of many sugars and sugar alcohols (erythrulose, arabinose, xylose, inosose, galactose, talopyranose, fucose, erythritol, and ribitol), organic acids (propanoic acid, 2,3-dihydroxybutanoic acid, palmitic acid, linolenic acid, and galacturonic acid), and other metabolites (2-oxazoline, silane, and glycine) in white clover...In addition, the campesterol and stigmasterol significantly accumulated in all plants in spite of the DA-6 pretreatment under drought stress, which could be an important adaptive response to water deficit due to beneficial roles of those two metabolites in regulating cell membrane stability and antioxidant defense. Present findings provide new evidence of DA-6-regulated metabolic homeostasis contributing to drought tolerance in leguminous plants."

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=81 | Active, not recruiting | Sponsor: ML Bio Solutions, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Muscular Dystrophy

Metabolism of Malus halliana Roots Provides Insights into Iron Deficiency Tolerance Mechanisms. (PubMed, Plants (Basel)) - "Carbohydrates (digalacturonate, L-xylitol, ribitol, D-xylulose, glucose, and glycerol) are degraded into pyruvate through glycolysis and pentose phosphate, which participate in the TCA...This study thoroughly examines the metabolite response to plant iron deficiency, highlighting the crucial roles of sugar metabolism, tricarboxylic acid cycle regulation, and glutathione metabolism in the short-term iron deficiency response of apples. It also lays the groundwork for future research on analyzing iron deficiency tolerance."

Journal • Hematological Disorders

Cyberlindnera qingyuanensis f.a., sp. nov., a yeast species isolated from rotting wood. (PubMed, Int J Syst Evol Microbiol) - "galapagoensis by its ability to grow in cellobiose, l-rhamnose, ribitol, galactitol, and dl-lactate, its growth at 37 °C, and its inability to ferment raffinose. The Mycobank number is MB 854693."

Journal

Exploring genetic associations in systemic lupus erythematosus through Mendelian randomization: implications for novel biomarkers and therapeutic targets. (PubMed, Clin Rheumatol) - "Four biomarkers were identified as having significant associations with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI levels [odds ratio (OR), 1.379; 95% confidence interval (CI), 1.180 to 1.613; FDR, 0.046], IL-17A levels (OR, 2.197; 95% CI, 1.412 to 3.418; FDR, 0.044), N-acetyl-aspartyl-glutamate (NAAG) levels (OR, 0.882; 95% CI, 0.831 to 0.936; FDR, 0.030), and ribitol levels (OR, 0.743; 95% CI, 0.644 to 0.857; FDR, 0.012)...• The findings suggest that NAAG levels have a protective effect against SLE, partly mediated through IL-17A, indicating a complex interplay between these biomarkers in the pathogenesis of SLE. • Intersectional analysis across multiple datasets revealed 29 biomarkers with consistent effects on SLE risk, highlighting new directions for future research and potential personalized therapeutic strategies."

Biomarker • Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • IL17A

Quantitative determination of C-polysaccharide in Streptococcus pneumoniae capsular polysaccharides by enzyme-linked immunosorbent assay. (PubMed, J Immunol Methods) - "The sensitivity of the ELISA method is higher because the sample is used directly unlike HPAEC-PAD method where sample is subjected to harsh treatment, such as acid digestion and quantify C-Ps based on peak area of ribitol or AAT. Furthermore, 1H NMR and HPAEC-PAD are expensive and laborious methods. Our work, underscores the simple and efficient ELISA that can be used for quantification of C-Ps in pneumococcal polysaccharide preparations."

Journal • Infectious Disease • Pneumococcal Infections • Pneumonia