Publications by authors named "Damsker J"
Pembrolizumab-induced Myasthenia Gravis and Myocarditis.
J Community Hosp Intern Med Perspect
May 2024
As the use of immune checkpoint inhibitors (ICPi) such as pembrolizumab is rapidly expanding in the field of immuno-oncology, it is crucial for healthcare providers to be aware of their immune-related adverse events (irAE) which are thought to be driven by augmented immune response of T-cells. While neurologic irAE are underrepresented in literature, their consequences could lead to fatal outcomes. In this report, we describe the case of a patient with excellent performance status prior to pembrolizumab therapy who subsequently suffered myasthenic crisis eventually requiring tracheostomy and long-term mechanical ventilation.
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- * Vamorolone, a drug for Duchenne muscular dystrophy, is metabolized by specific enzymes (CYP3A4, CYP3A5, UGT1A1), and this study looks at its pharmacokinetics in young boys with DMD.
- * Analysis found that the pharmacokinetics of vamorolone were consistent across subjects, and genetic variations in the enzymes studied did not significantly affect how the drug was processed in their bodies.
Article Synopsis
- Vamorolone, a glucocorticoid receptor agonist, was tested to assess its effectiveness and safety over 48 weeks compared to prednisone in children with Duchenne muscular dystrophy (DMD).
- A double-blind clinical trial involved 121 participants aged 4 to under 7 years, receiving varying doses of vamorolone and prednisone, with improvements monitored in motor skills and growth.
- Results indicated that vamorolone (6 mg/kg/day) maintained motor skill improvements over 48 weeks, with significant growth benefits seen after participants switched from prednisone to vamorolone.
Article Synopsis
- Long-term use of corticosteroidal anti-inflammatory drugs can negatively impact patient quality of life, highlighting the need for safer alternatives.
- The study tested vamorolone, a new type of dissociative steroid, for its effectiveness and safety in boys aged 4 to under 7 with Duchenne muscular dystrophy (DMD) over a 24-week period.
- Results showed that vamorolone (6 mg/kg) significantly improved motor function compared to placebo, while the safety profile was potentially better than traditional corticosteroids.
Article Synopsis
- Vamorolone is a synthetic steroid that shows strong anti-inflammatory effects, and earlier studies indicated it improved motor function in boys with Duchenne muscular dystrophy (DMD) after 6 months of high-dose treatment.
- This study aimed to evaluate the outcomes of 30 months of ongoing vamorolone treatment in DMD patients, conducted by the Cooperative International Neuromuscular Research Group across multiple locations.
- Results indicated that while the mean time-to-stand velocity of participants on higher doses of vamorolone showed a slight decrease over the treatment period, this change was not statistically significant, suggesting the need for further research.
Article Synopsis
- Vamorolone is a new investigational drug for treating Duchenne muscular dystrophy (DMD) that aims to reduce muscle weakness without some of the negative effects seen with long-term corticosteroid use.
- In an 18-month study involving participants aged 4 to 7, vamorolone showed significant clinical improvements in motor functions compared to baseline measurements.
- The study also compared outcomes from vamorolone-treated patients with those on no corticosteroids and those already receiving corticosteroid treatment, finding similar improvements in standing ability for vamorolone and corticosteroid-naïve participants.
Article Synopsis
- Duchenne muscular dystrophy is a genetic disorder that causes progressive damage to muscles, leading to early death, and current steroid treatments have significant side effects, particularly bone loss.
- A new drug called vamorolone has been developed that modifies the steroid structure to maintain effectiveness while significantly reducing these negative side effects.
- Research reveals that vamorolone's unique properties are due to its partial agonism, which disrupts specific interactions within the glucocorticoid receptor, resulting in targeted effects on muscle regulation without compromising other important functions.
Article Synopsis
- The study evaluated vamorolone, a novel anti-inflammatory drug, in 48 boys aged 4-7 with Duchenne muscular dystrophy (DMD) to determine the optimal dosage and effectiveness.
- Conducting a 24-week trial with varying doses (0.25, 0.75, 2.0, and 6.0 mg/kg/d), researchers found that the 2.0 mg/kg/d dose significantly improved muscle function without the common side effects associated with glucocorticoids.
- Results indicated that vamorolone was safe and well-tolerated, showing potential benefits in bone health and lower risk of adrenal suppression and insulin resistance compared to traditional glucocorticoid treatments.
Article Synopsis
- - This study aimed to evaluate the effects of vamorolone, a novel steroid, on inflammation in a mouse model of arthritis, specifically after the disease has begun rather than before.
- - The research used 84 mice, with treatments (vamorolone or prednisolone) given orally for 7 days post-disease onset, assessing disease severity, joint inflammation, and inflammation markers.
- - Results showed that vamorolone significantly reduced inflammation and joint damage compared to prednisolone, suggesting it could be a safer and effective treatment option for rheumatoid arthritis and similar conditions.
Article Synopsis
- Cardiomyopathy is a major concern in Duchenne muscular dystrophy, with mineralocorticoid and glucocorticoid receptors playing distinct roles in heart and muscle issues.
- The drug vamorolone can act as an MR antagonist and a unique GR ligand, reducing inflammation and offering better safety compared to prednisone.
- In studies on mice, vamorolone effectively prevents harmful effects linked to MR activation, unlike prednisolone, which worsens symptoms of cardiomyopathy.
Article Synopsis
- Duchenne muscular dystrophy (DMD) is a genetic disorder affecting boys, caused by mutations in the dystrophin gene, for which vamorolone is being studied as a treatment.
- Vamorolone shows favorable pharmacokinetics (PK) with a half-life of about 2 hours and a maximum plasma concentration occurring 2-4 hours after dosing, with consistent results in both healthy men and boys with DMD.
- The drug is absorbed better when taken with food, exhibits dose-linear pharmacokinetics without drug accumulation during daily dosing, and has similar clearance rates in both populations.
Glucocorticoids are standard of care for many chronic inflammatory conditions, including juvenile dermatomyositis (JDM) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We sought to define pharmacodynamic biomarkers of therapeutic efficacy and safety concerns of glucocorticoid treatment for these two disorders. Previous proteomic profiling of patients with Duchenne muscular dystrophy (DMD) and inflammatory bowel disease (IBD) treated with glucocorticoids identified candidate biomarkers for efficacy and safety concerns of glucocorticoids.
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- The study investigates vamorolone, a new type of steroidal anti-inflammatory drug, in boys aged 4 to under 7 with Duchenne muscular dystrophy over a 2-week period.
- The results show that vamorolone was safe and well-tolerated, with improved safety profiles such as reduced insulin resistance and adrenal suppression compared to traditional glucocorticoids.
- The research also indicated that vamorolone has potential anti-inflammatory effects, suggesting it could preserve the benefits of steroids while minimizing their negative side effects, with further studies planned to explore clinical outcomes.
Article Synopsis
- Corticosteroids are effective anti-inflammatory drugs, but their chronic use leads to harmful side effects, especially in children, prompting research for safer alternatives like vamorolone (VBP15).
- Vamorolone, a dissociative glucocorticoid receptor ligand, shows similar anti-inflammatory effects as traditional steroids without the negative side effects, as demonstrated in the mdx mouse model of Duchenne muscular dystrophy (DMD).
- The study found that vamorolone primarily reduces pro-inflammatory miRNAs, whereas prednisolone activates miRNAs linked to steroid side effects; both treatments influence the inflammatory transcription factor NF-κB, highlighting potential new biomarkers and drug targets.
Article Synopsis
- * A preclinical trial evaluated the effects of two corticosteroids, vamorolone (dissociative) and prednisolone (conventional), on inflammation and organ dysfunction in sickle cell disease mice.
- * While both corticosteroids reduced inflammation and white blood cell counts, they also caused significant liver damage, highlighting possible risks of hepatic toxicity despite reduced inflammation in sickle cell disease patients.
Article Synopsis
- - Vamorolone (VBP15) is a new type of glucocorticoid drug that effectively reduces inflammation without many side effects commonly seen with traditional glucocorticoids, like prednisone.
- - In clinical trials, Vamorolone was shown to be well-tolerated by healthy adults, with a similar metabolism to prednisone but significantly less impact on adrenal function and side effects like bone fragility or immune suppression.
- - The unique structure of Vamorolone allows it to bind to glucocorticoid and mineralocorticoid receptors differently than existing drugs, which may explain its reduced side effects while retaining anti-inflammatory properties.
Article Synopsis
- Corticosteroids like dexamethasone are commonly used in neuro-oncology for their anti-inflammatory effects, but many patients suffer from negative side effects.
- This study explored vamorolone, a new steroid alternative, in a mouse model to see if it could reduce harmful side effects while maintaining anti-inflammatory benefits.
- Results showed that vamorolone effectively reduced pro-inflammatory signals like dexamethasone, but had a better safety profile, improving activity and survival in mice compared to those treated with dexamethasone.
Objective: Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial.
Methods: We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect.
Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.
View Article and Find Full Text PDFWhat is the central question of this study? What is the functional relevance of OPN isoform expression in muscle pathology? What is the main finding and its importance? The full-length human OPN-a isoform is the most pro-inflammatory isoform in the muscle microenvironment, acting on macrophages and myoblasts in an RGD-integrin-dependent manner. OPN-a upregulates expression of tenascin-C (TNC), a known Toll-like receptor 4 (TLR4) agonist. Blocking TLR4 signalling inhibits the pro-inflammatory effects of OPN-a, suggesting that a potential mechanism of OPN action is by promoting TNC-TLR4 signalling.
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- - The study aimed to evaluate the effects of VBP15, a steroidal compound, on reducing inflammation and symptoms of colitis in mice, as well as its impact on growth in juvenile mice.
- - Experiments involved treating human intestinal epithelial cells with VBP15 and administering it to mice with induced colitis over specific periods to compare its effects against prednisolone.
- - Results showed that VBP15 significantly reduced inflammatory markers and colitis symptoms, while causing less growth stunting compared to prednisolone, suggesting it could be a safer treatment for inflammatory bowel disease.
Article Synopsis
- Overproduction of mucins in inflammatory lung diseases worsens health outcomes, with a focus on the mucin gene MUC5AC being regulated by inflammatory mediators like IL-1β and glucocorticoid drugs such as Dexamethasone (Dex).
- VBP15, a compound from ReveraGen BioPharma, shows promise as an anti-mucin agent by suppressing MUC5AC gene expression without some of the side effects associated with long-term steroid use.
- Experimental results indicate that VBP15 effectively reduces MUC5AC levels in human airway epithelial cells through mechanisms involving the glucocorticoid receptor (GR) and inhibition of NFκB, differing from the action of Dex.
Article Synopsis
- Mitotic synchrony is the normal, synchronized division of cells, but asthmatic airway epithelial cells show mitotic asynchrony, which contributes to inflammation.
- A study compared the effects of traditional glucocorticoids with a new drug, VBP15, on mitotic synchrony and inflammatory responses in these asthmatic cells after mechanical injury.
- VBP15 not only improved mitotic synchrony but also significantly reduced key inflammatory and fibrogenic cytokines, suggesting it may be more effective and safer for treating asthma than traditional glucocorticoids.
Article Synopsis
- - Multiple sclerosis is a chronic autoimmune disease that damages the central nervous system through inflammation and demyelination, often treated with glucocorticoids like prednisolone, which have significant side effects.
- - A new compound called VBP15 has shown promise in treating multiple sclerosis with fewer side effects while effectively reducing disease severity and inflammation, particularly in mouse models.
- - VBP15 was found to inhibit harmful pro-inflammatory gene expression in human macrophages without the bone loss and muscle atrophy related to prednisolone, indicating its potential as a safer treatment option.
Mitotic asynchrony induces transforming growth factor-β1 secretion from airway epithelium.
Am J Respir Cell Mol Biol
September 2014
We recently proposed that mitotic asynchrony in repairing tissue may underlie chronic inflammation and fibrosis, where immune cell infiltration is secondary to proinflammatory cross-talk among asynchronously repairing adjacent tissues. Building on our previous finding that mitotic asynchrony is associated with proinflammatory/fibrotic cytokine secretion (e.g.
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