Planning a Phase 1 Clinical Trial: Target Product Profile for a Novel Target CAR T-cell Therapy

https://openworks.mdanderson.org/sumexp21/1013/thumbnail.jp

The 2023 pipeline of disease-modifying antirheumatic drugs (DMARDs) in clinical development for spondyloarthritis (including psoriatic arthritis): a systematic review of trials

Objectives The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for spondyloarthritis (SpA) in the coming years.Methods We conducted a systematic review of 17 national and international clinical trial databases for all disease-modifying antirheumatic drugs (DMARDs) for SpA that are already marketed, in clinical development or withdrawn. The search was performed on February 2023 with the keywords “spondyloarthritis”, “ankylosing spondylitis” and “psoriatic arthritis”. For each molecule, we only considered the study at the most advanced stage of clinical development.Results Concerning axial SpA (axSpA), a total of 44 DMARDs were identified: 6 conventional synthetic DMARDs (csDMARDs), 27 biological DMARDs (bDMARDs) and 11 targeted synthetic DMARDs (tsDMARDs). Among the 18 targeted treatments (b+tsDMARDs) in current development, corresponding trials reached phase I (n=1), II (n=10) and III (n=7). Ten molecules are IL-17 inhibitors, two Janus kinase (JAK) inhibitors and two granulocyte-macrophage colony-stimulating factor inhibitors; four have another mode of action. Concerning psoriatic arthritis (PsA), 44 DMARDs were identified: 5 csDMARDs, 27 bDMARDs and 12 tsDMARDs. Among the 15 molecules in current development, corresponding trials reached phase II (n=8) and III (n=7). Six molecules are JAK inhibitors, six IL-17 inhibitors and one an IL-23 inhibitor; two have another mode of action.Conclusion This systematic review identified 18 and 15 molecules in clinical development for axSpA and PsA, respectively, which suggests a strengthening of the therapeutic arsenal in the coming years. However, with so many DMARDs but low target diversity, we will need to develop strategies or biomarkers to help clinicians make informed treatment decisions

Respiratory gated multistatic PET reconstructions: feasibility and interest for the radiotherapy of moving lung tumours

International audienc

Staphylococcus aureus bloodstream infection in patients with prosthetic joint included in the prospective VIRSTA cohort study: frequency and time of occurrence of periprosthetic joint infection

International audienceAmong 143 patients of the VIRSTA cohort study with Staphylococcus aureus bacteremia and an arthroplasty implanted for more than a year, S. aureus periprosthetic joint infection was observed in 19%. Signs of infection (pain and swelling) were always present, in median 1 day (range, 0-21 days) after onset of bacteremia. Staphylococcus aureus has both a high potential for metastatic infection and a high affinity for foreign material. Possible prosthesis infection is of clinical concern in all patients with preexisting prosthetic materials experiencing S. aureus bloodstream infection (SAB). Prosthetic joints are especially prone to infection during the course of bacteremia, with a risk of infection much higher with S. aureus than with other microorganisms, 20% vs 7%, in a recent prospective study [1]. As early intervention with debridement in prosthetic joint infection (PJI) is paramount to retain the implant and to prevent infection relapse; eliminating PJI after SAB is important. However, additional data are needed to better describe the clinical characteristics of PJI after SAB in particular time lapses and whether systematic imaging of the prosthesis could be necessary after SAB. We described the frequency and clinical presentation of PJIs observed among patients with prosthetic joints implanted for >1 year before bacteremia and enrolled in the VIRSTA study, a multicenter prospective cohort study of patients with SAB

Clinical respiratory motion correction software (reconstruct, register and averaged—RRA), for 18 F-FDG-PET-CT: phantom validation, practical implications and patient evaluation

International audienceOn fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) CT of pulmonary or hepatic lesions, standard uptake value (SUV) is often underestimated due to patient breathing. The aim of this study is to validate, on phantom and patient data, a motion correction algorithm [reconstruct, register and averaged (RRA)] implemented on a PET-CT system

Prospective comparison of FDG PET/CT and diffusion-weighted MRI for para-aortic metastases detection in cancer of the uterine cervix.

International audienc

Chronic sodium bromide treatment relieves autistic-like behavioral deficits in three mouse models of autism

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behavior. To date, no pharmacological treatment has been approved that ameliorates social behavior in patients with ASD. Based on the excitation/inhibition imbalance theory of autism, we hypothesized that bromide ions, long used as an antiepileptic medication, could relieve core symptoms of ASD. We evaluated the effects of chronic sodium bromide (NaBr) administration on autistic-like symptoms in three genetic mouse models of autism: Oprm1 -/- , Fmr1 -/- and Shank3 Δex13-16-/- mice. We showed that chronic NaBr treatment relieved autistic-like behaviors in these three models. In Oprm1 -/- mice, these beneficial effects were superior to those of chronic bumetanide administration. At transcriptional level, chronic NaBr in Oprm1 null mice was associated with increased expression of genes coding for chloride ions transporters, GABAA receptor subunits, oxytocin and mGlu4 receptor. Lastly, we uncovered synergistic alleviating effects of chronic NaBr and a positive allosteric modulator (PAM) of mGlu4 receptor on autistic-like behavior in Oprm1 -/- mice. We evidenced in heterologous cells that bromide ions behave as PAMs of mGlu4, providing a molecular mechanism for such synergy. Our data reveal the therapeutic potential of bromide ions, alone or in combination with a PAM of mGlu4 receptor, for the treatment of ASDs

Value of SPECT-CT lymphoscintigraphy for preoperative detection and anatomic location of sentinel lymph nodes in vulvar cancer.

International audienc

Value of SPECT-CT lymphoscintigraphy for preoperative detection and anatomic location of sentinel lymph nodes in vulvar cancer.

International audienc