ASP1128 / Astellas - LARVOL DELTA

Plasticity of Root System Architecture and Whole Transcriptome Responses Underlying Nitrogen Deficiency Tolerance Conferred by a Wild Emmer Wheat QTL. (PubMed, Plant Cell Environ) - "This included Jasmonic acid metabolism, a key hormone mediating RSA plasticity (AOS1, TIFY, MTB2, MYC2), and lignification-mediated root strengthening (CYP73A, 4CL). 'N-metabolism' was identified as a main shared pathway to IL99 and Ruta, with enhanced nitrate uptake predominant in IL99 (NRT2.4), while remobilisation was the main strategy in Ruta (NRT2.3). These findings provide novel insights into wheat plasticity response underlying tolerance to N-deficiency and demonstrate the potential of WEW for improving N-uptake under suboptimal conditions."

Journal

The Effects of Peroxisome Proliferator-Activated Receptor-Delta Modulator ASP1128 in Patients at Risk for Acute Kidney Injury Following Cardiac Surgery. (PubMed, Kidney Int Rep) - "No safety issues were identified with ASP1128 treatment, but rates of postoperative atrial fibrillation were lower (11.6%) than in the placebo group (29.6%). ASP1128 was safe and well-tolerated in patients at risk for AKI following cardiac surgery, but it did not show efficacy in renal endpoints."

Clinical • Journal • Surgery • Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Nephrology • Renal Disease • Reperfusion Injury • IGFBP7 • TIMP2

Single- and Multiple-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP1128, a Novel Peroxisome Proliferator-activated Receptor δ Modulator, in Healthy Participants. (PubMed, Clin Pharmacol Drug Dev) - "ASP1128 treatment led to rapid and dose-related upregulation of six fatty acid oxidation-related PPARδ target genes at ≥10 mg, which lasted >24 hours postdose. In conclusion, single and multiple intravenous doses of ASP1128 were generally well tolerated, with dose-dependent pharmacokinetics and target gene engagement in healthy participants."

Journal • PK/PD data • Acute Kidney Injury • Cardiovascular • Dermatology • Nephrology • Renal Disease • Reperfusion Injury

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury (AKI) Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2 | N=351 | Completed | Sponsor: Astellas Pharma Inc | N=151 ➔ 351

Enrollment change • Acute Kidney Injury • Nephrology

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2; N=151; Completed; Sponsor: Astellas Pharma Inc; Active, not recruiting ➔ Completed

Clinical • Trial completion • Acute Kidney Injury • Nephrology

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2; N=151; Active, not recruiting; Sponsor: Astellas Pharma Inc; Recruiting ➔ Active, not recruiting; N=220 ➔ 151; Trial completion date: Mar 2022 ➔ Oct 2021; Trial primary completion date: Jan 2022 ➔ Jul 2021

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Kidney Injury • Nephrology

A Study of MA-0217 (ASP1128) in Healthy Adult Subjects and Healthy Elderly Subjects (clinicaltrials.gov) - P1; N=102; Completed; Sponsor: Astellas Pharma Europe B.V.

Clinical • New P1 trial

Whole-Genome Sequencing of Two Moroccan Mycobacterium tuberculosis Strains. (PubMed, Microbiol Resour Announc) - "In Morocco, the spread of multidrug-resistant (MDR) tuberculosis (TB) has become a major challenge. Here, we announce the draft genome sequences of two Mycobacterium tuberculosis strains, MTB1 and MTB2, isolated from patients with pulmonary tuberculosis in Morocco, to describe variants associated with drug resistance."

Journal • Infectious Disease • Respiratory Diseases • Tuberculosis

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2; N=220; Recruiting; Sponsor: Astellas Pharma Inc; Trial completion date: Sep 2020 ➔ Mar 2022; Trial primary completion date: Jul 2020 ➔ Jan 2022

Clinical • Trial completion date • Trial primary completion date • Acute Kidney Injury • Nephrology

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2; N=220; Recruiting; Sponsor: Astellas Pharma Inc; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Kidney Injury • Chronic Kidney Disease • Nephrology

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2; N=220; Active, not recruiting; Sponsor: Astellas Pharma Inc; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Comparing IS6110-RFLP, PGRS-RFLP and IS6110-Mtb1/Mtb2 PCR methods for genotyping of Mycobacterium tuberculosis isolates. (PubMed, J Appl Microbiol) - "The study showed that IS6110-Mtb1/Mtb2 PCR, which is a simple and economical MTB genotyping approach, could be a more appropriate method to be applied in the low-budget research programs."

Journal • Infectious Disease • Tuberculosis

Termination in Jasmonate Signaling by MYC2 and MTBs. (PubMed, Trends Plant Sci) - "The master regulator MYC2, interacting with MED25, has been shown to be deactivated by the bHLH transcription factors MTB1, MTB2, and MTB3. An autoregulatory negative feedback loop has been proposed for this termination in JA signaling."

Journal

MYC2 Regulates the Termination of Jasmonate Signaling via an Autoregulatory Negative Feedback Loop. (PubMed, Plant Cell) - "Here, we report an unexpected function of MYC2 in regulating the termination of JA signaling through activating a small group of JA-inducible bHLH proteins, termed MYC2-TARGETED BHLH1 (MTB1), MTB2, and MTB3. Therefore, MYC2 and MTB proteins form an autoregulatory negative feedback circuit to terminate JA signaling in a highly organized manner. We exemplify that new gene editing tools, such as CRISPR/Cas9, open up new avenues to exploit MTB genes for crop protection."

Journal

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2; N=220; Recruiting; Sponsor: Astellas Pharma Inc; Initiation date: Jul 2019 ➔ Nov 2019

Trial initiation date

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2; N=220; Recruiting; Sponsor: Astellas Pharma Inc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Tuberculosis transmission in the population of patients from the Krakow Region (Poland) based on the epidemiological and molecular methods. (PubMed, Int J Mycobacteriol) - "The genome DNA of 275 Mycobacterium tuberculosis (Mtb) strains from tuberculosis patients, inhabitants of the city of Krakow, was subjected to a genetic analysis via the spoligotyping method and the IS6110-Mtb1-Mtb2 polymerase chain reaction (PCR) method. Active transmission of tuberculosis occurs largely among the individuals maintaining probably periodic contacts. The patients who are in the risk groups may play an important role in the transmission of tuberculosis."

Clinical • Journal

Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (clinicaltrials.gov) - P2; N=220; Not yet recruiting; Sponsor: Astellas Pharma Inc

Clinical • New P2 trial