Joenja (leniolisib)
Research Synopsis
- Joenja (leniolisib) is an oral drug specifically designed to treat activated phosphoinositide 3-kinase delta syndrome (APDS), a genetic immune disorder characterized by immune dysregulation.
- The drug received its first approval in March 2023 for patients aged 12 and older and is currently under review in the European Union.
- A randomized, placebo-controlled phase 3 trial demonstrated that leniolisib significantly improved lymph node size and increased naive B cell levels, indicating enhanced immune function with fewer adverse effects compared to placebo.
- Research shows leniolisib selectively inhibits the PI3Kδ isoform, leading to promising safety and efficacy profiles for improving immune health in APDS patients.
- Leniolisib treatment has been associated with decreased infection rates and a reduction in the need for supplemental immunoglobulin therapy among treated patients.
- Findings from case studies indicate leniolisib effectively resolved IgA vasculitis symptoms in patients with APDS, highlighting its potential for addressing related immune complications.
- Qualitative studies emphasize the significant burden of APDS on patients and their caregivers, with leniolisib providing a new hope for better management of this condition.
- Leniolisib has distinct advantages over traditional therapies like sirolimus, showing more targeted effects and improving outcomes for patients suffering from immune deficiencies associated with APDS.
- Future research may expand the understanding of leniolisib's effects beyond APDS as it explores its application in similar immune dysregulation issues.
Joenja (leniolisib)
Editorial: Immune dysregulation in inborn errors of immunity.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
X-Linked Lymphoproliferative Disease Mimicking Multisystem Inflammatory Syndrome in Children-A Case Report.
London, UK
2 hours ago
1 Received
- - Most children with SARS-CoV-2 have mild or no symptoms, but a small group develops a serious inflammatory condition known as MIS-C, which resembles other severe immune responses.
- - A case study describes a boy with MIS-C who showed unusual lab results and ultimately suffered from severe complications, including fatal liver failure linked to EBV-associated HLH, despite receiving multiple treatments.
- - The diagnosis of X-linked lymphoproliferative disease type 1 (XLP1) post-mortem suggests that doctors should consider HLH in severe MIS-C cases for better treatment strategies and genetic counseling.
$100 - $150
Hourly Rate
Cellular Mechanisms Underlying B Cell Abnormalities in Patients With Gain-of-Function Mutations in the Gene.
London, UK
2 hours ago
1 Received
- APDS is a genetic immune disorder caused by specific mutations, leading to immunodeficiency and issues with B cell regulation, characterized by high transitional B cells, B cell loss, and increased serum IgM levels.!* -
- A study of 24 APDS patients discovered that their B cells are larger, exhibit higher death rates, impaired class switching, but maintain normal plasmablast differentiation, alongside unusual secretion patterns of antibodies.!* -
- Findings indicate that the reduced number of B cells is likely due to increased naïve B cell death, while a larger population of specific B cells shows enhanced activation and differentiation, ultimately causing high IgM levels due to impaired class switching.!*
$100 - $150
Hourly Rate
A randomized, placebo-controlled phase 3 trial of the PI3Kδ inhibitor leniolisib for activated PI3Kδ syndrome.
London, UK
2 hours ago
1 Received
- Activated phosphoinositide 3-kinase delta syndrome (APDS) is an immune disorder that leads to various health issues like infections and autoimmunity due to overactive PI3Kδ signaling.
- A phase 3 clinical trial tested leniolisib, a specific inhibitor of PI3Kδ, on 31 patients aged 12 and older, comparing its effects against a placebo over 12 weeks.
- Results showed that leniolisib significantly reduced lymph node size and increased naïve B cells, indicating improved immune function, while also being well-tolerated with fewer adverse events compared to placebo.
$100 - $150
Hourly Rate
PI3king apart a rare disease with targeted therapy.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Structure-guided semi-rational design of an imine reductase for enantio-complementary synthesis of pyrrolidinamine.
London, UK
2 hours ago
1 Received
- The study focuses on engineered imine reductases (IREDs) developed through structure-guided semi-rational design to enhance their effectiveness in chemical reactions.
- Key amino acid residues W234 and F260 were identified as crucial for modifying stereoselectivity, leading to the creation of two new variants with high enantio-selectivity.
- These variants demonstrated exceptional performance in synthesizing pyrrolidinamines and were successfully applied to produce important drug intermediates efficiently from commercially available materials.
$100 - $150
Hourly Rate
The hyperinflammatory spectrum: from defects in cytotoxicity to cytokine control.
London, UK
2 hours ago
1 Received
- Cytotoxic lymphocytes kill target cells by releasing cytotoxic granules, and dysfunction in this pathway can lead to dangerous conditions like hemophagocytic lymphohistiocytosis (HLH) in both humans and mice.
- HLH is characterized by an excessive immune response rather than direct viral effects, where prolonged interaction between immune cells causes overproduction of pro-inflammatory cytokines like interferon gamma.
- Recent research has identified new genetic causes of HLH, highlighting the active roles of target cells and macrophages in the disease, which could guide future treatments for HLH and related immune dysfunctions.
$100 - $150
Hourly Rate
ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome.
London, UK
2 hours ago
1 Received
- - Activated phosphoinositide 3-kinase δ syndrome (APDS) is a type of immunodeficiency that causes various health issues, including frequent infections and problems with immune regulation like autoimmune diseases and cancer.
- - Autoimmunity is often one of the first signs of immune issues in disorders like APDS, and it's important to recognize the range of autoimmune symptoms associated with these conditions.
- - Advances in understanding the genetic and molecular bases of APDS have led to new treatments, like leniolisib, which aim to improve patient outcomes by addressing the underlying immune dysregulation.
$100 - $150
Hourly Rate
Human PIK3R1 mutations disrupt lymphocyte differentiation to cause activated PI3Kδ syndrome 2.
London, UK
2 hours ago
1 Received
- Heterozygous mutations in PIK3R1 cause activated PI3Kδ syndrome 2 (APDS2), which shares symptoms with APDS1 caused by PIK3CD mutations.
- Research using a CRISPR/Cas9 mouse model and patient immune cells revealed that PIK3R1 mutations lead to unique cellular defects, including issues with B cell function and survival of pups.
- The study found important differences in how PIK3R1 loss-of-function (LOF) and PIK3CD gain-of-function (GOF) mutations affect immune cell signaling and function, highlighting distinct genetic impacts on immune health.
$100 - $150
Hourly Rate
Leniolisib: First Approval.
London, UK
2 hours ago
1 Received
- Leniolisib (JOENJA) is an oral drug developed by Pharming Group NV to treat immunodeficiency disorders, specifically targeting a protein called PI3Kδ.
- It received its first approval in March 2023 for treating activated PI3Kδ syndrome (APDS) in patients aged 12 and older and is currently under review in the EU for the same condition.
- Development for treating Sjögren's syndrome has been stopped; this article outlines the key milestones leading to leniolisib's approval for APDS.
$100 - $150
Hourly Rate
Leniolisib Phosphate.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Inborn errors of human B cell development, differentiation, and function.
London, UK
2 hours ago
1 Received
- B cells, which originate from stem cells in bone marrow, play crucial roles in immune regulation and produce antibodies to combat invading pathogens.* -
- These B cells create memory cells for a quick response to future infections and plasma cells that continuously release antibodies, helping maintain long-term immunity.* -
- Research on individuals with genetic defects in B cell function provides valuable insights into immune cell development, disease mechanisms, and advancements in our understanding of human humoral immunity.*
$100 - $150
Hourly Rate
Modulating the PI3K Signalling Pathway in Activated PI3K Delta Syndrome: a Clinical Perspective.
London, UK
2 hours ago
1 Received
- Activated phosphoinositide-3-kinase δ syndrome (APDS) is a genetic immune disorder caused by mutations that lead to overactivation of the PI3Kδ pathway, resulting in immune dysregulation.
- Treatment strategies have evolved to not only include supportive therapies but also focus on modulating the PI3K pathway, with sirolimus being one effective option.
- The recent introduction of specific PI3Kδ inhibitors like leniolisib shows promising results and may offer a more targeted treatment approach compared to traditional methods, particularly in relation to immune conditions versus blood cancers.
$100 - $150
Hourly Rate
PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond.
London, UK
2 hours ago
1 Received
- The PI3K pathway is important for various cellular functions, especially in immune cell development, and its activity is regulated by specific isoforms like PI3Kδ.
- A genetic condition called activated phosphoinositide 3-kinase δ syndrome (APDS) results from the overactivity of PI3Kδ, leading to immune system issues.
- Among the treatments tested, leniolisib stands out for its effectiveness and safety, as it selectively inhibits the δ isoform without significant side effects that have been seen with other inhibitors.
$100 - $150
Hourly Rate
Interim analysis: Open-label extension study of leniolisib for patients with APDS.
London, UK
2 hours ago
1 Received
- Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is a genetic condition characterized by overactive PI3Kδ, leading to immune issues like recurrent infections and autoimmunity.
- Leniolisib, a targeted inhibitor of PI3Kδ, showed promise in improving immune function and reducing complications like lymphoproliferation in patients with APDS over a 12-week period.
- An ongoing study involving 37 patients showed that most experienced mild to moderate side effects, but leniolisib significantly decreased infection rates and improved overall health, with many patients needing less immunoglobulin therapy.
$100 - $150
Hourly Rate
Diagnostic evaluation of paediatric autoimmune lymphoproliferative immunodeficiencies (ALPID): a prospective cohort study.
London, UK
2 hours ago
1 Received
- The study investigates autoimmune lymphoproliferative syndrome (ALPS) and similar severe conditions characterized by lymphoproliferation and autoimmune cytopenias, aiming to better classify these disorders based on genetic and clinical features.
- Conducted in Germany with 431 children referred for ALPS evaluation, the study categorized patients based on specific criteria related to lymphoproliferation and associated immune deficiencies, with a median diagnostic age of about 9.8 years.
- Findings revealed that 55% of enrolled children were diagnosed with ALPS, and genetic assessments helped differentiate ALPS from autoimmune lymphoproliferative syndrome-like diseases, enhancing understanding and classification of these immune disorders.
$100 - $150
Hourly Rate
Leniolisib: a novel treatment for activated phosphoinositide-3 kinase delta syndrome.
London, UK
2 hours ago
1 Received
- The text presents the inhibition constant (IC) values for different PI3K isoforms.
- It indicates that PI3Kδ is the most potent with an IC of 11 nM, suggesting strong inhibition.
- In contrast, PI3Kγ has the least potency with an IC of 2,230 nM, indicating weaker inhibition.
$100 - $150
Hourly Rate
Disruption of DLL4/NOTCH1 Causes Dysregulated PPARγ/AKT Signaling in Pulmonary Arterial Hypertension.
London, UK
2 hours ago
1 Received
- Pulmonary arterial hypertension (PAH) is a serious lung condition caused by changes in small blood vessels that lead to increased pressure in the pulmonary artery, and this is often linked to problems in the cells lining these vessels.
- A key factor, DLL4, helps maintain healthy blood vessels through NOTCH1 signaling, and its inhibition is connected to the advancement of PAH, but the exact process is not fully understood.
- Research indicates that restoring DLL4/NOTCH1 signaling or inhibiting the AKT pathway can help reverse harmful changes in the blood vessels seen in PAH, offering potential treatment strategies using compounds like leniolisib.
$100 - $150
Hourly Rate
APDS patients with immune-complex vasculitis and resolution with leniolisib.
London, UK
2 hours ago
1 Received
- Activated phosphoinositide 3-kinase delta syndrome (APDS) is a genetic immune disorder characterized by various immune issues, including infections and autoimmune responses.
- This text presents a case series of three patients with APDS who developed refractory IgA vasculitis, a type of immune-mediated inflammation not previously linked to APDS patients.
- Treatment with leniolisib, an FDA-approved drug for APDS, successfully resolved the IgA vasculitis, suggesting that patients with immune dysregulation, like IgA vasculitis, should be tested for APDS.
$100 - $150
Hourly Rate
A qualitative study to explore the burden of disease in activated phosphoinositide 3-kinase delta syndrome (APDS).
London, UK
2 hours ago
1 Received
- Activated phosphoinositide 3-kinase delta syndrome (APDS) is an extremely rare immunodeficiency affecting only 256 people worldwide, prompting a study to understand the disease's effects from the viewpoints of patients and caregivers.
- The study involved qualitative interviews with healthcare providers, individuals with APDS, and caregivers, focusing on symptoms, health-related quality of life (HRQoL), and personal experiences, alongside a narrative account exercise completed by some participants.
- Findings revealed that APDS leads to various clinical symptoms like frequent infections and fatigue, severely impacting daily activities, emotional well-being, and the quality of life for both patients and their caregivers.
$100 - $150
Hourly Rate