Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive fibrotic lung disease resulting in increasing shortness of breath, cough, and low oxygen levels as a result of lung tissue scarring . The goal of this open-label (no placebo) study is to evaluate the safety and tolerability of artesunate at three different doses in patients with IPF. The secondary goals are to explore the blood biomarkers present in IPF patients at the beginning of the study and to study how those biomarkers change following treatment with artesunate. Participants will have 7 visits to the study site over 20 weeks which will include physician exams, vital signs, questionnaires, research and safety blood samples, and taking artesunate capsules by mouth for 12 weeks.
Artesunate is used world-wide for the treatment of severe malaria but has also been found to block specific proteins that cause lung scarring and may provide an additional treatment to slow the fibrotic process in the lung and improve survival and quality of life for patients with IPF.

Start Date01 May 2025

Sponsor / Collaborator

Stanford University

NCT05441410 / Not yet recruitingPhase 1/2IIT

Comparing Safety and Protective Efficacy of the Whole Plasmodium Falciparum Sporozoite Chemoprophylaxis Vaccine Candidate PfSPZ-CVac and Prime- Target Vaccination With Viral Vectored Vaccine Candidate Regime MVA ME-TRAP/ ChAd63 ME-TRAP in Malaria-naïve, Healthy Adult Volunteers in Germany

This is a single centre, randomized, placebo-controlled phase 1/2 study comparing two malaria vaccine candidates. The first vaccine candidate PfSPZ-CVac (Plasmodium falciparum sporozoites (PfSPZ) challenge administered with a chemoprophylactic antimalarial) will be chemoattenuated in vivo with the antimalarial Pyramax. The second vaccine candidate is prime- target vaccination with viral vectored vaccine candidate regime MVA ME-TRAP (Modified Vaccinia Ankara (MVA) multiple epitope thrombosponin-related adhesion protein (ME-TRAP)) and ChAd63 ME-TRAP (Chimpanzee adenovirus 63 (ChAd63). The safety and protective efficacy of both vaccine candidates will be to assessed by controlled human malaria infection with PfSPZ Challenge strain NF54 administered intravenously by syringe.

Start Date01 Oct 2024

Sponsor / Collaborator

University Hospital Tübingen

[+2]

100 Clinical Results associated with SERCA2 x ATP2A1

100 Translational Medicine associated with SERCA2 x ATP2A1

0 Patents (Medical) associated with SERCA2 x ATP2A1

169

Literatures (Medical) associated with SERCA2 x ATP2A1

01 Mar 2024·Biomedicine & Pharmacotherapy

Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats

Article

Author: Salagre, D ; Alcázar-Navarrete, B ; Gómez-Moreno, G ; Villalón-Mir, M ; Navarro-Alarcón, M ; Agil, A ; Tamimi, F

Melatonin acute treatment limits obesity of young Zücker diabetic fatty (ZDF) rats by non-shivering thermogenesis (NST). We recently showed melatonin chronically increases the oxidative status of vastus lateralis (VL) in both obese and lean adult male animals. The identification of VL skeletal muscle-based NST by uncoupling of sarcoendoplasmic reticulum Ca²⁺-ATPase (SERCA)- sarcolipin (SLN) prompted us to investigate whether melatonin is a SERCA-SLN calcium futile cycle uncoupling and mitochondrial biogenesis enhancer. Obese ZDF rats and lean littermates (ZL) of both sexes were subdivided into two subgroups: control (C) and 12 weeks orally melatonin treated (M) (10 mg/kg/day). Compared to the control groups, melatonin decreased the body weight gain and visceral fat in ZDF rats of both sexes. Melatonin treatment in both sex obese rats restored the VL muscle skin temperature and sensitized the thermogenic effect of acute cold exposure. Moreover, melatonin not only raised SLN protein levels in the VL of obese and lean rats of both sexes; also, the SERCA activity. Melatonin treatment increased the SERCA2 expression in obese and lean rats (both sexes), with no effects on SERCA1 expression. Melatonin increased the expression of thermogenic genes and proteins (PGC1-α, PPARγ, and NRF1). Furthermore, melatonin treatment enhanced the expression ratio of P-CaMKII/CaMKII and P-AMPK/AMPK. In addition, it rose mitochondrial biogenesis. These results provided the initial evidence that chronic oral melatonin treatment triggers the CaMKII/AMPK/PGC1α axis by upregulating SERCA2-SLN-mediated NST in ZDF diabetic rats of both sexes. This may further contribute to the body weight control and metabolic benefits of melatonin.

26 Sep 2023·Cells

Polyarginine Cell-Penetrating Peptides Bind and Inhibit SERCA2.

Article

Author: Martinsen, Marita ; Louch, William E ; Lunde, Per Kristian ; Lunde, Marianne ; Manfra, Ornella ; Støle, Thea Parsberg ; Carlson, Cathrine Rein

Cell-penetrating peptides (CPPs) are short peptide sequences that have the ability to cross the cell membrane and deliver cargo. Although it is critical that CPPs accomplish this task with minimal off-target effects, such actions have in many cases not been robustly screened. We presently investigated whether the commonly used CPPs TAT and the polyarginines Arg₉ and Arg₁₁ exert off-target effects on cellular Ca²⁺ homeostasis. In experiments employing myocytes and homogenates from the cardiac left ventricle or soleus muscle, we observed marked inhibition of Ca²⁺ recycling into the sarcoplasmic reticulum (SR) following incubation with polyarginine CPPs. In both tissues, the rate of SR Ca²⁺ leak remained unchanged, indicating that protracted Ca²⁺ removal from the cytosol stemmed from inhibition of the SR Ca²⁺ ATPase 2 (SERCA2). No such inhibition occurred following treatment with TAT, or in preparations from the SERCA1-expressing extensor digitorum longus muscle. Experiments in HEK cells overexpressing individual SERCA isoforms confirmed that polyarginine incubation specifically inhibited the activity of SERCA2a and 2b, but not SERCA1 or 3. The attenuation of SERCA2 activity was not dependent on the presence of phospholamban, and ELISA-based analyses rather revealed direct interaction between the polyarginines and the actuator domain of the protein. Surface plasmon resonance experiments confirmed strong binding within this region of SERCA2, and slow dissociation between the two species. Based on these observations, we urge caution when employing polyarginine CPPs. Indeed, as SERCA2 is expressed in diverse cell types, the wide-ranging consequences of SERCA2 binding and inhibition should be anticipated in both experimental and therapeutic settings.

01 Sep 2023·Acta physiologica (Oxford, England)

FiNuTyper: Design and validation of an automated deep learning-based platform for simultaneous fiber and nucleus type analysis in human skeletal muscle.

Article

Author: Chapman, Mark A ; Emanuelsson, Eric B ; Petri, Susanne ; Reitzner, Stefan M ; Han, Nan S ; Shirokova, Vera ; Bergmann, Olaf ; Lundquist, August ; Druid, Henrik ; Lázár, Enikő ; Sundberg, Carl J ; Alkass, Kanar

While manual quantification is still considered the gold standard for skeletal muscle histol. anal., it is time-consuming and prone to investigator bias.To address this challenge, we assembled an automated image anal. pipeline, FiNuTyper (Fiber and Nucleus Typer).We integrated recently developed deep learning-based image segmentation methods, optimized for unbiased evaluation of fresh and postmortem human skeletal muscle, and utilized SERCA1 and SERCA2 as type-specific myonucleus and myofiber markers after validating them against the traditional use of MyHC isoforms.Parameters including cross-sectional area, myonuclei per fiber, myonuclear domain, central myonuclei per fiber, and grouped myofiber ratio were determined in a fiber-type-specific manner, revealing that a large degree of sex- and muscle-related heterogeneity could be detected using the pipeline.Our platform was also tested on pathol. muscle tissue (ALS and IBM) and adapted for the detection of other resident cell types (leukocytes, satellite cells, capillary endothelium).In summary, we present an automated image anal. tool for the simultaneous quantification of myofiber and myonuclear types, to characterize the composition and structure of healthy and diseased human skeletal muscle.

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