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Primary CoQ10 deficiency is a rare mitochondrial disorder that impacts fewer than one in 100,000 individuals. Credit: StudioMolekuul via Shutterstock. BPGbio has received a Rare Pediatric Disease Designation from the US Food and Drug Administration (FDA) for BPM31510IV to treat primary coenzyme Q10 deficiency, an ultra-rare mitochondrial disorder. Primary CoQ10 deficiency affects fewer than one in 100,000 people. It hampers the body’s ability to produce CoQ10, a molecule crucial for cellular energy production and biomembrane stabilisation. The deficiency can lead to severe developmental delays, weakness of muscle, seizures, and potentially fatal organ damage, with symptoms often appearing in early childhood. Oral CoQ10 supplements failed to reach therapeutic levels in severely affected organs. BPGbio’s BPM31510IV has shown potential in addressing this gap, leveraging the company’s NAi Interrogative Biology platform, which combines patient biology with AI-driven analysis. See Also: Potential for peptides to replace antibodies in radiopharma, says WuXi AppTec exec BPGbio’s mitochondrial disorder drug gets paediatric disease status It is not only a lead candidate for solid tumours such as glioblastoma multiforme and pancreatic cancer but also shows promise for various rare diseases. BPGbio president and CEO Niven Narain said: “BPM31510 has been developed in topical, IV and oral formulations and is a prime example of the power of our biology-first approach to drug discovery and development, illustrating the powerful predictive capabilities of our NAi Interrogative Biology platform, and the benefit of validating AI-derived predictions through wet lab experiments and in vivo modelling. “By using hypothesis-free causal AI to analyse vast amounts of biological data, we were able to uncover and validate new potential applications BPM31510, including its potential to address mitochondrial diseases like primary CoQ10 deficiency.” BPGbio’s investigational treatment has also received orphan drug designation for glioblastoma multiforme, pancreatic cancer, and epidermolysis bullosa, in addition to the rare pediatric disease designation for primary CoQ10 deficiency.

SAN FRANCISCO--( BUSINESS WIRE )-- BIOMAKERS , a Precision Medicine & Biotech Company that supports data-driven Drug Development globally, and TOPAZIUM , an AI-driven healthtech company specializing in drug discovery and human wellbeing, have announced the results of their innovative collaborative project. This partnership showcases the power of AI systems in leveraging real-world DNA sequencing data to identify novel targets aimed at improving the efficacy of immunotherapy for non-small cell lung cancer (NSCLC) treatment. The findings were presented at the prestigious 2024 American Society of Clinical Oncology (ASCO) meeting in Chicago. The study used Whole Exome Sequencing (WES) data from biopsies of squamous and adenocarcinoma NSCLC processed through BIOMAKERS ' advanced DNA sequencing platforms. The data was then analyzed using GFPrint™, a proprietary algorithm developed by TOPAZIUM , that generates virtual representations of tumor exomes in a latent space defined by the genetic features of the samples. “The advent of drugs targeting the PD-1/PD-L1 axis has revolutionized NSCLC treatment. Although promising, individual responses to these therapies can vary, and we believe this ongoing project will help to better understand mechanisms involved in PD1/PD-L1 expression, optimize treatment protocols, and identify which patients are most likely to benefit from these therapies. In this study, DNA sequencing and GFPrint™ were employed to identify mutations in genes linked to PD-L1 expression in NSCLC adenocarcinoma tumor samples,” said Dr. Rubén Salanova, Chief Medical Officer & Co-Founder of BIOMAKERS . “Using this strategy, we have identified a subpopulation of adenocarcinoma patients with increased PD-L1 expression levels, enriched in non-silent mutations of 10 genes of interest, mostly included in the HIF-1α signaling pathway. Notably, 6 of these mutated genes (PIK3R1, HK1, NOS2, NRAS, BRAF, ITGA1) were uniquely found in adenocarcinomas” said Juan Manuel Domínguez, Head of Preclinical & Biostatistics at TOPAZIUM . “All these newly identified genes deserve further studies to validate them as potential targets for pharmacological intervention concomitant with PD-1/PD-L1 blockade, and as potential biomarkers for patient selection to improve the efficiency of immunotherapy in NSCLC treatment,” added Andrea Mendoza, Head of R&D at BIOMAKERS . For more details, the abstract can be accessed at: https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13600 For more information about GFPrint™, visit: https://www.biorxiv.org/content/10.1101/2024.03.08.584090v4 About BIOMAKERS: BIOMAKERS is an Oncology Precision Medicine Company with a Comprehensive Genomic Platform and reach throughout LATAM, delivering care-changing solutions. In addition to its strong focus on physician support and patient care, their Life Science division partners with biopharma companies to advance R&D programs by providing support for Drug Discovery and Drug Development. This innovative work is enabled by direct partnerships with renowned Health Institutions across 17 different countries. contacto@biomakers.net About TOPAZIUM: TOPAZIUM is committed to supporting medical research with artificial intelligence (AI) through state-of-the-art analytical tools. They have developed a comprehensive AI engine that utilizes multiple medical data types to assist in identifying new disease patterns and the most promising therapeutic approaches, striving to achieve one of the most challenging global goals: health for all. info@topazium.com

MXene nanoparticle scaffolds have been shown to stimulate muscle growth, making them a promising option to treat muscle loss and damage. Now, researchers explain the molecular mechanisms behind their positive influence on muscle regeneration. This discovery can advance MXene scaffolds, potentially improving muscle reconstruction surgeries and establishing them as a standard medical practice for muscle recovery. Tissue engineering, which involves the use of grafts or scaffolds to aid cell regeneration, is emerging as a key medical practice for treating volumetric muscle loss (VML), a condition where a significant amount of muscle tissue is lost beyond the body's natural regenerative capacity. To improve surgical outcomes, traditional muscle grafts are giving way to artificial scaffold materials, with MXene nanoparticles (NPs) standing out as a promising option. MXene NPs are 2D materials primarily composed of transition-metal carbides and nitride. They are highly electrically conductive, can accommodate a wide range of functional groups, and have stacked structures that promote cell interactions and muscle growth. While there have been practical demonstrations in the laboratory showcasing their ability to promote the reconstruction of skeletal muscles, the specific mechanism by which they do so remains unclear. To address this gap, Associate Professor Yun Hak Kim from the Department of Anatomy and Department of Biomedical Informatics alongside Professors Suck Won Hong, and Dong-Wook Han from the Department of Cogno-Mechatronics Engineering at Pusan National University, developed nanofibrous matrices containing MXene NPs as scaffolds. They used DNA sequencing to reveal the genes and biological pathways activated by MXene NPs to aid in muscle regeneration. These findings, published on 4 January 2024, in Volume 16 of Nano-Micro Letters, mark a significantly advancement in the use of MXene scaffolds for treating muscle damage. "This discovery posits a prospective avenue for the utilization of these materials to augment the efficacy of muscle tissue regeneration post-injury or damage," explains Professor Kim. In the initial phase, the team created a nanofibrous PCM matrix containing poly(lactide-co-ε-caprolactone) (P), reinforced with collagen (C), and Ti3C2Tx MXene nanoparticles (M). To determine the specific effect of MXene NPs on muscle growth, they prepared three controls: pristine PLCL (P), PLCL with Collagen (PC), and PLCL with MXene (PM). On testing all the scaffolds on mouse models with induced volumetric muscle loss, the researchers observed a significant increase in the overall number of muscle cells in PCM-treated mice compared to the other groups. To understand how MXene nanoparticles (NPs) impact muscle regeneration and growth at the molecular level, the researchers introduced C2C12 myoblasts, which are precursors of muscle cells, onto PC and PCM matrices. The objective was to analyze the differences in gene expression levels between the two matrices. Within the PCM matrix, a heightened production of inducible nitric oxide synthase (iNOS) and serum/glucocorticoid-regulated kinase 1 (SGK1) was identified-two proteins closely associated with calcium signaling and muscle regeneration. These results suggest that MXenes promote calcium ion (Ca2+) deposition around cells. This heightened levels of intracellular Ca2+ triggers the activation of genes that produce iNOS and SGK1 proteins. SGK1 influences the mTOR-AKT pathway, promoting cell proliferation, survival, and myogenesis-the conversion of myoblasts to muscle fibers. Simultaneously, iNOS increases the production of nitric oxide (NO), contributing to myoblast proliferation and muscle fiber fusion. The combined effects lead to the development of mature muscle tissue. The aligned PCM nanofibrous matrices offer biophysical cues for intracellular biochemical signaling, guiding myogenic behaviors. This discovery contributes to our understanding of MXene's potential to regrow muscle and holds promise for refining scaffold designs to enhance this process further. "Within 5 to 10 years, this research may yield groundbreaking treatments for muscle injuries. MXene NP-infused matrices could become a routine in medical practice for athletes, people with muscle-related ailments, and those recuperating from muscle-related traumas or surgeries," Prof. Kim optimistically states. 'These NPs might enhance muscle regeneration methods, offering improved outcomes for reconstructive surgeries and conditions like muscular dystrophy, where muscle function is compromised,' he further adds. The MXene NP-infused matrices hold potential for customization to meet diverse needs in treating muscle loss injuries. This customization may involve adjusting composition, structure, or properties to match specific patient requirements, like size, shape, or bioactivity enhancement. Tailoring these materials could offer personalized solutions for various muscle loss severities. Additionally, the observed enhanced muscle regeneration could aid in a more efficient recovery, potentially reducing post-treatment rehabilitation needs. These matrices, with controllable mechanical properties, hold promise for enhancing in vivo muscle regeneration. Further research into MXene promises expanded clinical applications, potentially benefiting human well-being.