Publications by authors named "Annamaria De Luca"
Article Synopsis
- The study compares the gene expression of two mouse models for DMD: the BL10-mdx, which shows mild symptoms, and the more accurate D2-mdx, focusing on their respective muscles and organs over time.
- It identifies specific reference genes (like CSNK2A2 and AP3D1) that provide reliable data for monitoring disease progression, emphasizing the necessity for validated reference genes in genetic research.
Article Synopsis
- * The main health risks associated with TSC include brain tumors, sudden unexpected death due to epilepsy, and respiratory issues, which lead to significant morbidity and mortality.
- * While there are therapies available for TSC, there's a need for more research into its neurological effects and for developing new treatment options, including the repurposing of existing drugs and targeting new mechanisms.
Mexiletine is the first choice drug in the treatment of non-dystrophic myotonias. However, 30% of patients experience little benefit from mexiletine due to poor tolerability, contraindications and limited efficacy likely based on pharmacogenetic profile. Safinamide inhibits neuronal voltage-gated sodium and calcium channels and shows anticonvulsant activity, in addition to a reversible monoamine oxidase-B inhibition.
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- Effective post-marketing surveillance of drugs and vaccines is crucial for assessing their safety and effectiveness in real-world settings.
- Spontaneous reporting from healthcare professionals and the public is a key method for identifying rare adverse drug reactions (ADRs) and adverse events following immunization (AEFIs).
- The growing use of electronic health records and interconnected databases enables large-scale evaluations, helping to generate real-world evidence that informs pharmacovigilance and regulatory decisions.
Article Synopsis
- The study focuses on two siblings who inherited two new variants (N935Y and H1393Q) in the Nav1.1 sodium channel, leading to a drug-responsive neurological condition while their parents remain asymptomatic.
- Most variants in this channel are usually inherited heterozygously, but in this case, both siblings express a biallelic (two copies) inheritance pattern.
- Functional analyses of sodium currents show that these variants reduce channel activity by about 20%, potentially contributing to their illness, but also suggest that other factors could play a role in the disease's development.
Article Synopsis
- Heart failure (HF) is a significant global health issue, especially for the aging population; this study investigates the drug sacubitril/valsartan's effects on aging-related HF with preserved ejection fraction (HFpEF) in rats.
- After 12 weeks of treatment, both sacubitril/valsartan and valsartan showed improvements in cardiac hypertrophy, evidenced by reduced heart muscle thickness, but neither treatment effectively reduced myocardial fibrosis or corrected diastolic dysfunction.
- The study indicates that while the treatments positively impacted heart muscle size and activated cardioprotective signaling pathways, challenges like inflammation and oxidative stress remained unaddressed, leaving diastolic dysfunction and fibrosis in aging hearts.
Article Synopsis
- Aging leads to sarcopenia, characterized by loss of muscle strength and increased fatigue, partially due to reduced essential amino acid intake affecting muscle health.
- A study shows that branched-chain amino acid (BCAA) supplements can improve muscle weakness and atrophy in aged mice, particularly when combined with L-alanine.
- Findings indicate that calcium homeostasis is disrupted in aged muscles, but BCAAs, especially the BCAAs+L-alanine combination, can restore some of these calcium-related dysfunctions, highlighting their potential in addressing age-related muscle decline.
Article Synopsis
- Oral anticoagulant therapy for atrial fibrillation includes traditional vitamin K antagonists like warfarin and newer direct-acting oral anticoagulants (DOACs) such as dabigatran and rivaroxaban, with DOACs being preferred due to lower bleeding risks.
- Anticoagulant switching from warfarin to DOACs is a common practice, but understanding the implications of this switch, especially for patients with both atrial fibrillation and heart failure, remains crucial.
- A machine learning analysis was conducted to examine the effects of switching from warfarin to DOACs in heart failure patients with atrial fibrillation, highlighting the positive impacts of DOACs beyond just preventing blood clots
Article Synopsis
- Myogenesis, the process of forming and regenerating skeletal muscle, can be significantly disrupted in Duchenne muscular dystrophy (DMD) due to lack of dystrophin, a key cytoskeletal protein.
- Research involved comparing two types of mouse muscle cell lines, one normal (wild-type) and one dystrophic, to analyze changes in ion channel activity and gene expression during muscle differentiation.
- Findings showed increased inward current density and altered gene expression in dystrophic cells, suggesting that ion channels could be potential targets for treatment and biomarkers for monitoring muscle development in DMD.
Article Synopsis
- Myasthenia gravis (MG) is a rare autoimmune disorder that leads to significant muscle weakness due to problems with nerve-to-muscle communication.
- Most patients develop autoantibodies against the acetylcholine receptor, leading to standard treatments like acetylcholinesterase inhibitors and immunomodulating agents (e.g., corticosteroids).
- The review aims to summarize the latest five approved pharmacological treatments for MG, highlighting both preclinical and clinical trial evidence, and discusses new approaches like complement blockade and neonatal Fc receptor antagonism.
Article Synopsis
- * TISBE (TIRESIA Improved on Structure-Based Explainability) is a new online tool that enhances testing with a larger dataset, an explainable AI framework, a new consensus classifier, and improved methods for prediction reliability.
- * With a training set of 1,008 chemicals and very high sensitivity and specificity, TISBE can identify molecular fragments related to a chemical's toxicity and is freely accessible to users.
Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.
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- Brugada syndrome (BrS) is a complex inherited cardiac condition recognized since 1992, posing challenges in diagnosis, risk assessment for arrhythmias, and management.
- Approximately 20% of individuals with BrS have genetic variants, but a growing understanding of its polygenic nature suggests the use of polygenic risk scores for better individual risk prediction.
- Current research aims to uncover biomarkers for diagnosing and managing BrS, advocating for a comprehensive model that considers clinical, genetic, and environmental factors to improve patient outcomes.
The potential role of liver kinase B1 (LKB1) in the altered activation of the master metabolic and epigenetic regulator adenosine monophosphate-activated protein kinase (AMPK) in Duchenne muscular dystrophy has not been investigated so far. Hence, we analyzed both gene and protein levels of LKB1 and its related targets in gastrocnemius muscles of adult C57BL/10 mdx mice and D2 mdx mice, a model with a more severe dystrophic phenotype, as well as the sensitivity of the LKB1-AMPK pathway to AMPK activators, such as chronic exercise. Our data show, for the first time, a reduction in the levels of LKB1 and accessory proteins, MO25 and STRADα, in both mdx strains versus the respective wild type, which was further impaired by exercise, in parallel with a lack of further phosphorylation of AMPK.
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- SGLT2 inhibitors (gliflozins) are gaining attention as a treatment for heart failure with reduced left ventricular ejection fraction (HFrEF), but their full effects on heart function remain unclear.
- A study involving 78 diabetic patients used machine learning to analyze how well these medications worked, revealing specific echocardiographic parameters that could predict the treatment response.
- The analysis indicated that while gliflozins helped improve heart remodeling and function, their effectiveness decreased with more severe heart damage, highlighting the importance of monitoring healthy heart metrics for better treatment outcomes.
Article Synopsis
- Growth hormone secretagogues (GHSs) have multiple functions, including activating specific receptors and controlling inflammation and metabolism, which may be beneficial for treating Duchenne muscular dystrophy (DMD).
- In a study with mice, two GHS compounds, EP80317 and JMV2894, showed improved muscle strength and reduced fibrosis when administered over eight weeks.
- Both treatments led to positive changes in muscle metabolism and gene expression, indicating potential new mechanisms for muscle recovery that do not rely on traditional pathways like IGF-1.
Ultrasonography is a safe, non-invasive imaging technique used in several fields of medicine, offering the possibility to longitudinally monitor disease progression and treatment efficacy over time. This is particularly useful when a close follow-up is required, or in patients with pacemakers (not suitable for magnetic resonance imaging). By virtue of these advantages, ultrasonography is commonly used to detect multiple skeletal muscle structural and functional parameters in sports medicine, as well as in neuromuscular disorders, e.
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- Sarcalumenin (SAR) is a calcium buffer protein primarily found in skeletal muscles and the heart, crucial for regulating calcium uptake and release during muscle contractions.
- SAR has a high capacity but low affinity for binding calcium and works alongside other calcium buffer proteins, influencing various physiological processes like SERCA stabilization and muscle fatigue resistance.
- Despite its similarities to the well-known calsequestrin, research on SAR is limited, and this review aims to highlight its importance in muscle function and potential involvement in muscle wasting disorders.
In age-related sarcopenia, the gradual loss of skeletal muscle mass, function and strength is underpinned by an imbalanced rate of protein synthesis/breakdown. Hence, an adequate protein intake is considered a valuable strategy to mitigate sarcopenia. Here, we investigated the effects of a 12-week oral supplementation with branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) with recognized anabolic properties, in 17-month-old (AGED) C57BL/6J male mice.
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- Cardiorenal syndrome involves heart and kidney issues that often arise from shared risk factors like hypertension and diabetes.
- A study on dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, showed it can improve kidney function and reduce markers of renal damage in a non-diabetic model of cardiorenal disease.
- The drug worked by decreasing inflammation, oxidative stress, and modifying the renin-angiotensin-aldosterone system, suggesting it offers protective benefits for renal health.
Article Synopsis
- Voltage-gated sodium channels are key targets for drug discovery due to their role in various physiological processes and disorders like epilepsy and chronic pain.
- In particular, myotonia is a condition that causes muscle stiffness from over-excitability of muscle fibers, and existing treatments include sodium channel blockers like mexiletine.
- The text emphasizes the need for more specific and effective drugs targeting the Na1.4 sodium channel isoform and discusses research on new compounds that may help treat myotonia.
The C57BL/10ScSn-Dmdmdx/J (mdx) mouse model has been used by researchers for decades as a model to study pathology of and develop therapies for Duchenne muscular dystrophy. However, the model is relatively mildly affected compared to the human situation. Recently, the D2.
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- - Researchers found a new mutation in the Kv1.1 gene linked to neurological issues like epilepsy and ataxia in a young girl, and noted that treatments with standard medications were initially ineffective.
- - The study aimed to understand how this specific mutation affects the function of the Kv1.1 channel by comparing it to the normal version, revealing that the mutation causes reduced potassium current and altered function.
- - Findings suggest that mutations in the Kv1.1 channel are associated with severe epilepsy, and highlight the effectiveness of certain medications, like acetazolamide, in treating conditions related to this channel's dysfunction.
ROS-activated cSrc tyrosine kinase (TK) promotes the degradation of β-dystroglycan (β-DG), a dystrophin-glycoprotein complex component, which may reinforce damaging signals in Duchenne muscular dystrophy (DMD). Therefore, cSrc-TK represents a promising therapeutic target. In mice, a 4-week subcutaneous treatment with dasatinib (DAS), a pan-Src-TKs inhibitor approved as anti-leukemic agent, increased muscle β-DG, with minimal amelioration of morphofunctional indices.
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