319 Results Found

This work is about how healthcare issues can be reframed from a sustainable and inclusive development perspective. Focusing on the case of orphan drugs and rare diseases, first, a country-based review of the main regulatory approaches to orphan drugs...

The retinoid-related orphan receptor α (RORα) is one subfamily of nuclear hormone receptors (NRs). This review summarizes the understanding and potential effects of RORα in the cardiovascular system and then analyzes current advance...

A better understanding of mechanistic insights into genes and enzymes implicated in rare diseases provide a unique opportunity for orphan drug development. Advances made in identification of synthetic lethal relationships between rare disorder genes...

Currently in Europe, approximately 30 million people suffer from rare diseases, and a major problem is that many patients do not have access to quality healthcare for their disorders. Moreover, there is also a lack of quality information and a networ...

Background and Objective: Orphan drugs have been a highlight of discussions due to their higher prices than non-orphan drugs. There is currently no European consensus on the method of value assessment for orphan drugs. This study assessed the relatio...

Human orphan genes are poorly annotated and lowly expressed, which makes their behavior in disease difficult to establish. We analyzed paired normal and disease RNA-seq libraries from four cohorts, quantified against a combined reference in which 219...

Asthma affects 10% of the worldwide population; about 5% of cases are severe with the need for target therapies such as biologics. All the biologics approved for asthma hit the T2 pathway of inflammation. T2-high asthma is classified as allergic and...

This paper assesses the impact of uncertainty for investors on the economic valuation of medical innovation projects for orphan drugs or rare diseases. Conventionally, investor evaluation uses the deterministic discounted cash flow (DCF) method with...

After Lithuania joined the European Union, the Regulation (EC) No. 141/2000 on orphan medicinal products and Commission Regulation (EC) No. 847/2000 came into force as part of national legislation. Member States must adopt specific measures to increa...

Background and aims: Orphan diseases, or rare diseases, are defined in Europe as diseases that affect less than 5 out of every 10,000 citizens. Given the small number of cases and the lack of profit potential, pharmaceutical companies have not invest...

Neurodegenerative disorders, particularly Alzheimer’s and Parkinson’s diseases, continue to challenge modern medicine despite therapeutic advances. Orphan G-protein-coupled receptors (GPCRs) have emerged as promising targets in the centra...

Background and Objective: This study assessed price differences by comparing annual treatment costs of similarly available orphan drugs in France, Germany, Italy, Norway, Spain, Sweden, and UK. Methods: Annual treatment costs per drug were calculated...

The historical insights and background of the discovery, development and clinical use of deferiprone (L1) and the maltol–iron complex, which were discovered over 40 years ago, highlight the difficulties, complexities and efforts in general orph...

While artificial intelligence has successful and innovative applications in common medicine, could its application facilitate research on rare diseases? This study explores the application of artificial intelligence (AI) in orphan drug research, focu...

Background: Claims included in package inserts (PIs) for medicinal products approved by the US Food and Drug Administration (FDA) constitute the regulatory definition of drugs’ benefits and risks. Objective: We sought to assess the usage of patient-r...

Background/Objectives: Orphan medicinal products offer essential treatments for rare diseases, but patient access varies across European Union countries despite a common regulatory framework. In Bulgaria, access is primarily through inclusion in the...

Traditionally, drug discovery utilises a de novo design approach, which requires high cost and many years of drug development before it reaches the market. Novel drug development does not always account for orphan diseases, which have low demand and...

Even if amyotrophic lateral sclerosis is still considered an orphan disease to date, its prevalence among the population is growing fast. Despite the efforts made by researchers and pharmaceutical companies, the cryptic information related to the bio...

Objective: The objective of this paper is to determine an upper price limit for an orphan drug by taken a broader perspective and, including also other monetary and non-monetary values for the society. Methods: This model is based on the expected fre...

Background and Objectives: Rare diseases (RDs) are life-threatening or chronically impairing conditions that affect about 6% of the world’s population. RDs are often called ‘orphan’ diseases, since people suffering from them attract...

Rare diseases are conditions that affect up to 65 people per 100,000 individuals. They are also known as “orphan diseases”, because they attract limited interest from researchers and pharmaceutical industries. Epidermolysis bullosa (EB),...

An increase in total drug (small molecules and biologics) approvals by the Food and Drug Administration (FDA) was seen in 2023 compared with the previous year. Cancer remained the disease most targeted by monoclonal antibodies (mAbs), followed by aut...

Oxysterols, important regulators of cholesterol homeostasis in the brain, are affected by neurodegenerative diseases. Early-onset Alzheimer’s disease is associated with higher levels of circulating brain-derived 24S-hydroxycholesterol (24S-OHC)...

Background: Babesiosis and malaria are infectious diseases caused by the intraerythrocytic parasites Babesia and Plasmodium, respectively. While no human red blood cell (RBC) receptors have been shown to be essential for B. microti (Bm) invasion, Duf...

G-protein-coupled receptors (GPCRs) are commonly pharmacologically modulated due to their ability to translate extracellular events to intracellular changes. Previously, studies have mostly focused on protein–protein interactions, but the focus...

Human papillomavirus (HPV) infections cause a significant proportion of cancers worldwide, predominantly squamous cell carcinomas (SCC) of the mucosas and skin. High-risk HPV types are associated with SCCs of the anogenital and oropharyngeal tract. H...

Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is an important transcription factor modulating gene transcription involved in endocrine control of liver metabolism. Transferrin receptor 2 (TFR2), a carrier protein for transferrin, is invo...

Testicular orphan receptors TR2 and TR4 serve as central regulators of erythropoiesis, orchestrating the entire continuum of erythroid progenitor cell proliferation, differentiation, and maturation. As core components of the direct repeat erythroid d...

Background: Multiple symmetric lipomatosis (MSL) is an orphan disease characterized by pathological expansion of lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT) areas, causing severe deformities and compression of vital organs. To dat...

This study examines patient access to orphan medicinal products (OMPs) in Central and Eastern Europe (CEE) over the past five years, focusing on seven countries: Bulgaria, Czechia, Hungary, Poland, Romania, Slovakia, and Slovenia. While these jurisdi...

The iron chelating orphan drug deferiprone (L1), discovered over 40 years ago, has been used daily by patients across the world at high doses (75–100 mg/kg) for more than 30 years with no serious toxicity. The level of safety and the simple, in...

Background: Orphan drugs (ODs) are pharmaceuticals manufactured for rare conditions that affect less than 200,000 people in the US. ODs are therefore produced in small quantities to meet sparse demand. Since 2010, OD shortages have become frequent, b...

The development of gene therapies for rare hereditary disorders is hindered by small patient cohorts, incomplete characterization of natural disease history, and the impracticality of conducting long-term clinical trials. Surrogate biomarkers—q...

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder which primarily affects the gastrointestinal and nervous systems. This disease is caused by mutations in the nuclear TYMP gene, which encodes for thymidi...

Importance: Neuroendocrine tumors (NETs) have traditionally been considered rare (orphan) diseases; however, improvements in diagnostic methods and heightened awareness about NETs may have altered their epidemiologic profile in the U.S. Objective: To...

Testicular receptor 4 (TR4, NR2C2) is an orphan nuclear receptor involved in the regulation of metabolism, inflammation, cardiovascular disease, and cancer. Accumulating evidence indicates that TR4 exhibits functional plasticity, exerting protective...

Retinoid-related orphan receptor γt (RORγt), a vital transcription factor for the differentiation of the pro-inflammatory Th17 cells, is essential to the inflammatory response and pathological process mediated by Th17 cells. Pharmacologic...

Background: Real-world evidence (RWE) can complement clinical trials to inform health technology assessments (HTAs). This study examined the extent to which RWE is considered in HTAs of non-oncology orphan medicinal products across six agencies globa...

Nuclear receptors (NRs) are transcription factors regulated by ligands that direct metabolism, development, and immunity. The NR superfamily constitutes a principal category of pharmacological targets for human ailments. Retinoic acid receptor-relate...

While great strides have been made in science and medicine ensuring better living standards and health care for most human beings, many issues still remain, which are responsible for an increase in mortality and morbidity rates of millions of people...

NDRG1 protein engages with the orphan nuclear receptor NR4A1, effectively suppressing the transcriptional activity of NF-κB and influencing the inflammatory response. However, the specific roles of the NDRG family and NR4A transcription factors...

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare autosomal recessive disorder of nucleoside metabolism that is caused by mutations in the nuclear thymidine phosphorylase gene (TYMP) gene, encoding for the enzyme thymidin...

Introduction: Idiosyncratic drug-induced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new drugs such as biotherapies outside the context of oncology. In the present paper, we report and discuss the clinical da...

Even though the application of Next-Generation Sequencing (NGS) has significantly facilitated the identification of disease-associated mutations, the diagnostic rate of rare diseases is still below 50%. This causes a diagnostic odyssey and prevents s...

Reaching a diagnosis and its communication are two of the most meaningful events in the physician–patient relationship. When facing a disease, most of the patients’ expectations rely on the hope that their clinicians would be able to unde...

Cohen syndrome is an autosomal recessive disorder caused by VPS13B (COH1) gene mutations. This syndrome is significantly underdiagnosed and is characterized by intellectual disability, microcephaly, autistic symptoms, hypotension, myopia, retinal dys...

Sex differences among patients with complement-gene-variant-mediated thrombotic microangiopathy (cTMA) are not well established. We examined demographic and clinical data from female and male patients with a history of cTMA enrolled in the Vienna thr...

The coincidence of two rare diseases such as congenital diaphragmatic hernia (CDH) and neuroblastoma is exceptional. With an incidence of around 2–3:10,000 and 1:8000 for either disease occurring on its own, the chance of simultaneous presentation of...

Glomerular kidney diseases typically begin insidiously and can progress to end stage kidney failure. Early onset of therapy can slow down disease progression. Early diagnosis is required to ensure such timely therapy. The goal of our study was to eva...

Background/Objectives: Rare diseases are a wide and heterogeneous group of multisystem life-threatening or chronically debilitating clinical conditions with reduced life expectancy and a relevant mortality rate in childhood. Some of these disorders h...