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Drugs Dec 2023Nedosiran (RIVFLOZA™), a once-monthly subcutaneous small interfering RNA (siRNA) therapy, is being developed by Dicerna Pharmaceuticals, a Novo Nordisk company, for... (Review)
Review
Nedosiran (RIVFLOZA™), a once-monthly subcutaneous small interfering RNA (siRNA) therapy, is being developed by Dicerna Pharmaceuticals, a Novo Nordisk company, for the treatment of primary hyperoxaluria (PH). It reduces oxalate overproduction by inhibiting the expression of the hepatic lactate dehydrogenase (LDH) enzyme. Nedosiran received its first approval on 29 September 2023 in the USA to lower urinary oxalate levels in children aged ≥ 9 years and adults with PH type 1 (PH1) and relatively preserved kidney function [e.g. estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m]. This article summarizes the milestones in the development of nedosiran leading to this first approval for PH1.
Topics: Child; Adult; Humans; Hyperoxaluria, Primary; Oxalates; Lactate Dehydrogenases; RNA, Small Interfering
PubMed: 38060091
DOI: 10.1007/s40265-023-01976-4 -
La Tunisie Medicale Jul 2023There are three types of primary hyperoxaluria, with type 1 considered the most severe.
INTRODUCTION
There are three types of primary hyperoxaluria, with type 1 considered the most severe.
AIM
To analyze the clinical, genetic, and evolutionary characteristics of type 1 primary hyperoxaluria with pediatric onset.
METHODS
This was a retrospective, descriptive study that included Tunisian children under the age of 18 at the time of diagnosis over a period of 25 years (January 1, 1996, to December 31, 2022).
RESULTS
Thirty-five patients were included, with a mean age of 4.1 years. The most common presenting circumstances of the disease were nephrolithiasis and end-stage renal failure. The average serum creatinine level was 225.42 µmol/l. Five mutations were identified, with the p.Ile244Thr mutation being the most prevalent. Nephrocalcinosis, surgical intervention, and a creatinine level ≥57 µmol/l were predictive of progression to end-stage renal failure. The infantile form was predictive of mortality.
CONCLUSIONS
Screening for the disease would improve the prognosis of this condition.
Topics: Child; Humans; Child, Preschool; Adult; Hyperoxaluria, Primary; Retrospective Studies; Kidney Failure, Chronic; Mutation
PubMed: 38445424
DOI: No ID Found -
Pharmaceuticals (Basel, Switzerland) Feb 2024A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of... (Review)
Review
A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. All oligonucleotides show chemically modified structures to enhance their stability and therapeutic effectiveness as antisense or aptamer oligomers. Some of them demonstrate various types of conjugation to driving ligands. The approved peptides comprise various structures, including linear, cyclic, and lipopeptides, and have diverse applications. Interestingly, the FDA has granted its first orphan drug designation for a peptide-based drug as a highly selective chemokine antagonist. Furthermore, Rett syndrome has found its first-ever core symptoms treatment, which is also peptide-based. Here, we analyze the TIDES approved in 2023 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects.
PubMed: 38399458
DOI: 10.3390/ph17020243 -
Orphanet Journal of Rare Diseases Aug 2023Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish... (Review)
Review
Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults. The clinical settings considered were arthralgia and joint stiffness as well as arthritis. Unspecific arthralgias are often the first symptoms of hereditary hemochromatosis, chronic low back pain may reveal an intervertebral disc calcification in relation with alkaptonuria, and progressive joint stiffness may correspond to a mucopolysaccharidosis or mucolipidosis. Gaucher disease is initially revealed by painful acute attacks mimicking joint pain described as "bone crises". Some IMD may induce microcrystalline arthropathy. Beyond classical gout, there are also gouts in connection with purine metabolism disorders known as "enzymopathic gouts". Pyrophosphate arthropathy can also be part of the clinical spectrum of Gitelman syndrome or hypophosphatasia. Oxalate crystals arthritis can reveal a primary hyperoxaluria. Destructive arthritis may be indicative of Wilson's disease. Non-destructive arthritis may be seen in mevalonate kinase deficiency and familial hypercholesterolemia.
Topics: Humans; Adult; Chondrocalcinosis; Gout; Joint Diseases; Metabolism, Inborn Errors; Hepatolenticular Degeneration
PubMed: 37563694
DOI: 10.1186/s13023-023-02810-6 -
Genes Aug 2023Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet,... (Review)
Review
Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet, microbiota, renal and metabolic disease) reasons underlie elevated plasma concentrations and tissue accumulation of oxalate, which is toxic to the body. A classic example is the triad of primary hyperoxaluria, nephrolithiasis, and kidney injury. Lessons learned from this example suggest further investigation of other putative factors associated with oxalate dysmetabolism, namely the identification of precursors (glyoxylate, aromatic amino acids, glyoxal and vitamin C), the regulation of the endogenous pathways that produce oxalate, or the microbiota's contribution to oxalate systemic availability. The association between secondary nephrolithiasis and cardiovascular and metabolic diseases (hypertension, type 2 diabetes, and obesity) inspired the authors to perform this comprehensive review about oxalate dysmetabolism and its relation to cardiometabolic toxicity. This perspective may offer something substantial that helps advance understanding of effective management and draws attention to the novel class of treatments available in clinical practice.
Topics: Humans; Oxalates; Diabetes Mellitus, Type 2; Hyperoxaluria, Primary; Kidney; Nephrolithiasis; Hypertension
PubMed: 37761859
DOI: 10.3390/genes14091719 -
Clinics and Research in Hepatology and... May 2024Enteric hyperoxaluria is a metabolic disorder resulting from conditions associated with fatty acid malabsorption and characterized by an increased urinary output of... (Review)
Review
Enteric hyperoxaluria is a metabolic disorder resulting from conditions associated with fatty acid malabsorption and characterized by an increased urinary output of oxalate. Oxalate is excessively absorbed in the gut and then excreted in urine where it forms calcium oxalate crystals, inducing kidney stones formation and crystalline nephropathies. Enteric hyperoxaluria is probably underdiagnosed and may silently damage kidney function of patients affected by bowel diseases. Moreover, the prevalence of enteric hyperoxaluria has increased because of the development of bariatric surgical procedures. Therapeutic options are based on the treatment of the underlying disease, limitation of oxalate intakes, increase in calcium salts intakes but also increase in urine volume and correction of hypocitraturia. There are few data regarding the natural evolution of kidney stone events and chronic kidney disease in these patients, and there is a need for new treatments limiting kidney injury by calcium oxalate crystallization.
Topics: Humans; Hyperoxaluria; Oxalates; Calcium Oxalate; Malabsorption Syndromes
PubMed: 38503362
DOI: 10.1016/j.clinre.2024.102322 -
Rhode Island Medical Journal (2013) Dec 2023Hyperoxaluria is a clinically relevant metabolic entity that portends a high morbidity burden. Primarily manifesting as kidney stone disease and chronic kidney disease,... (Review)
Review
Hyperoxaluria is a clinically relevant metabolic entity that portends a high morbidity burden. Primarily manifesting as kidney stone disease and chronic kidney disease, advanced hyperoxaluria can also affect major organs, including the brain, heart, liver, bone, and the skin. It is categorized based on etiology into primary and secondary hyperoxaluria. Pathology is attributed to excess de novo oxalate production in the former and multifactorial exogenous oxalate absorption or excess intake of its precursors in the latter. Diagnosis often involves demonstrating elevated urinary oxalate levels, especially in patients with normal kidney function. Here in this review, we will perform an in-depth discussion of various causes of hyperoxaluria and describe treatment options. In view of the significant morbidity burden associated with hyperoxaluria, patients could benefit from heightened clinician awareness to aid in the timely diagnosis and management of this condition.
Topics: Humans; Kidney Calculi; Hyperoxaluria; Oxalates
PubMed: 38015779
DOI: No ID Found