DeCure for Renal hypomagnesemia 5 with ocular involvement
DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for renal hypomagnesemia 5 with ocular involvement — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRenal hypomagnesemia 5 with ocular involvement maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for renal hypomagnesemia 5 with ocular involvement is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
Magnesium deficiency is under-recognised in clinical practice, and the kidney’s role in reabsorbing magnesium is central to several inherited disorders. Mutations in renal ion channels and transporters have been identified in Gitelman syndrome, familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC), familial hypomagnesaemia with secondary hypocalcaemia, autosomal dominant hypomagnesaemia with hypocalciuria, and autosomal recessive hypomagnesaemia. More recently, mutations in claudin-16/19, pro-epidermal growth factor, potassium channels Kv1.1 and Kir4.1, and hepatocyte nuclear factor 1B have been linked to hereditary hypomagnesaemia, acting through the transient receptor potential channel melastatin member 6 or by altering the driving force for magnesium influx.
A 2003 case report describes a 41-year-old man with hypomagnesaemia, hypercalciuria, nephrocalcinosis, myopia and horizontal nystagmus, diagnosed with FHHNC. He was treated with oral magnesium, chlorthalidone, potassium citrate and allopurinol for three years. Hypercalciuria improved, but serum magnesium could not be normalised. Renal function remained stable with mild insufficiency. The report notes that renal failure is common and end-stage renal disease can occur in children or young adults.
A 2021 report describes a paediatric patient with hypercalciuric hypomagnesaemia and bilateral chorioretinal atrophy. Whole exome sequencing revealed a homozygous c.223G>A (p.G75S) variant in CLDN19, previously reported only in compound heterozygosity. The authors state that ocular abnormalities are variable in patients with CLDN19 mutations, and that chronic kidney disease and retinal damage must be considered in this group. No treatment outcome or survival data are given for this patient.
What remains missing is a prospective trial testing any specific intervention in patients with renal hypomagnesaemia 5 with ocular involvement. No study has stratified patients by CLDN19 genotype or measured long-term renal and visual outcomes under a standardised regimen. Funding for such a trial and for systematic natural-history data collection is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Nephrology and Renovascular Disease · 2014 · 178 citations · open access
Hypomagnesemia: a clinical perspective
AbstractAlthough magnesium is involved in a wide spectrum of vital functions in normal human physiology, the significance of hypomagnesemia and necessity for its treatment are under-recognized and underappreciated in clinical practice. In the current review, we first present an overview of the clinical significance of hypomagnesemia and normal magnesium metabolism, with a focus on renal magnesium handling. Subsequently, we review the literature for both congenital and acquired hypomagnesemic conditions that affect the various steps in normal magnesium metabolism. Finally, we present an approach to the routine evaluation and suggested management of hypomagnesemia.
Current Opinion in Nephrology & Hypertension · 2016 · 80 citations
Mechanisms and causes of hypomagnesemia
AbstractPURPOSE OF REVIEW: Identification of the mechanisms of magnesium absorption and reabsorption has markedly enhanced our understanding of the causes of hypomagnesemia. RECENT FINDINGS: New gastrointestinal and renal causes of hypomagnesemia have been recently documented. SUMMARY: The recognition of new mechanisms and causes of magnesium absorption and reabsorption should enhance the ability to monitor patients at risk for hypomagnesemia and improve our ability to mitigate the serious symptoms associated with this disorder.
Pediatric Nephrology · 2008 · 65 citations · open access
Inherited forms of renal hypomagnesemia: an update
AbstractThe kidney plays an important role in ion homeostasis in the human body. Several hereditary disorders characterized by perturbations in renal magnesium reabsorption leading to hypomagnesemia have been described over the past 50 years, with the most important of these being Gitelman syndrome, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, familial hypomagnesemia with secondary hypocalcemia, autosomal dominant hypomagnesemia with hypocalciuria, and autosomal recessive hypomagnesemia. Only recently, following positional cloning strategies in affected families, have mutations in renal ion channels and transporters been identified in these diseases. In this short review, I give an update on these hypomagnesemic disorders. Elucidation of the genetic etiology and, for most of these disorders, also the underlying pathophysiology of the disease, has greatly increased our understanding of the normal physiology of renal magnesium handling. This is yet another example of the importance of studying rare disorders in order to unravel physiological and pathophysiological processes in the human body.
Current Opinion in Nephrology & Hypertension · 2010 · 30 citations
Novel molecular pathways in renal Mg2+ transport: a guided tour along the nephron
AbstractPURPOSE OF REVIEW: This review highlights recent advances in renal magnesium (Mg) handling. The understanding of the molecular processes of epithelial Mg transport has expanded considerably due to the identification of novel genes involved in hypomagnesemic disorders. RECENT FINDINGS: Mg deficiency remains one of the most common electrolyte disorders. Detailed genetic analysis of families with inherited forms of hypomagnesemia has led to the identification of new genes involved in Mg homeostasis. As such, familial hypomagnesemia has been linked to mutations in the claudin-16/19 complex located in the thick ascending limb. Moreover, the pro-epidermal growth factor, the potassium channels Kv1.1 and Kir4.1, and the hepatocyte nuclear factor 1B have recently been identified as causative factors in syndromes of hereditary hypomagnesemia. These proteins play key roles in regulating electrolyte balance within the distal convoluted tubule, either by directly affecting the epithelial Mg channel, transient receptor potential channel melastatin member 6, or by altering the driving force for Mg influx via the channel. SUMMARY: Recent genetic and molecular studies have further elucidated the processes that govern renal Mg transport and hence systemic Mg balance. This has provided us with new tools to understand the molecular pathology behind hypomagnesemia.
Scandinavian Journal of Urology and Nephrology · 2003 · 6 citations
Renal Hypomagnesemia, Hypercalciuria and Nephrocalcinosis in a Middle-aged Man
AbstractWe report a 41-year-old man with hypomagnesemia, hypercalciuria, nephrocalcinosis, myopia and horizontal nystagmus. The hypomagnesemia was due to primary renal magnesium loss. He was diagnosed as having the syndrome of renal hypomagnesemia, hypercalciuria and nephrocalcinosis. This is a rare condition generally diagnosed by the first to third decades of life. Renal failure is common and end-stage renal disease can occur in children or young adults. The patient was treated with oral magnesium, chlorthalidone, potassium citrate and allopurinol and was followed up for 3 years. Treatment resulted in an improvement in hypercalciuria but serum magnesium level could not be normalized. The patient's renal function remains stable, with a mild degree of renal insufficiency.
Journal of Pediatric Genetics · 2021 · 6 citations · open access
Familial Hypomagnesemia with Hypercalciuria, Nephrocalcinosis, and Bilateral Chorioretinal Atrophy in a Patient with Homozygous p.G75S Variant in CLDN19
AbstractAbstract Introduction Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare disorder caused by perturbation in renal reabsorption of magnesium and calcium. Biallelic pathogenic variants either in gene CLDN16 or CLDN19 are responsible for molecular defects. Most patients with CLDN19 variants have been associated with ocular involvements (FHHNCOI). Patient and Methods We had a pediatric patient with hypercalciuric hypomagnesemia and bilateral chorioretinal atrophy. Metabolic profiling and radiology examinations were performed, in addition to whole exome sequencing (WES) used for detection of the causative variant. Results Analysis of WES revealed a homozygous c.223G > A (p.G75S) variant in CLDN19. MutationTaster and Combined Annotation-Dependent Depletion support its deleterious effect and SHERLOC's criteria put it in pathogenic category. This variant is previously reported in compound heterozygous state with other known pathogenic variant. As far as we know, it is the first report of this variant in homozygous state. Conclusion The variant found in our patient is pathogenic and compatible with FHHNCOI characteristics. WES is an advantageous tool in molecular diagnosis and finding genetic pathology of this disease. In line with other reports, ocular abnormalities are variable in patients with CLDN19 mutations, and chronic kidney disease and retinal damages must be considered in this group.
The Clinical Spectrum of Acquired Hypomagnesemia: From Etiology to Therapeutic Approaches
AbstractHypomagnesemia is a frequent and often underrecognized electrolyte disturbance with important clinical consequences, especially in hospitalized and critically ill patients. This multifactorial condition arises from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications. Magnesium, the second most abundant intracellular cation, is crucial in enzymatic and physiological processes; its deficiency is associated with neuromuscular, cardiovascular, and metabolic complications. This narrative review focuses on the mechanisms and clinical consequences of drug-induced hypomagnesemia, highlighting the major drug classes involved such as diuretics, antibiotics, antineoplastic agents, and immunosuppressants. Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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