DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial primary hypomagnesemia — 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 moduleFamilial primary hypomagnesemia 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 familial primary hypomagnesemia 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.
Molecular view
ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) — ATP1A1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet y01drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7E20 · 2.7 Å · ligand CHOLESTEROL HEMISUCCINATE (Y01). Experimental structure, not a prediction.
What the evidence adds up to
Familial primary hypomagnesemia is caused by mutations in the TRPM6 gene, which encodes a channel that controls intestinal absorption and renal reabsorption of magnesium. One 2019 case report identified a novel homozygous missense mutation, p.(K1098E), in TRPM6 in a child from a consanguineous family who presented with seizures in the first weeks of life. In silico modelling suggested this variant disrupts stabilising TRP domain interactions. Both parents and two younger siblings carried the mutation heterozygously and had transient hypomagnesemia. A 2023 case report described a 5-month-old girl with a novel pathogenic TRPM6 variant who developed refractory seizures due to hypomagnesemia. The 2019 report states that management relies on prompt recognition, early magnesium replacement, and lifelong monitoring; the 2023 report similarly states treatment consists of administering high doses of magnesium throughout life.
A 2018 review of hypomagnesemia in critically ill patients notes that magnesium deficiency is mainly caused by gastrointestinal or renal disorders and can lead to secondary hypokalemia and hypocalcemia, as well as severe neuromuscular and cardiovascular manifestations. The review states there are limited studies to guide intermittent therapy of magnesium deficiency in critically ill patients, and that further clinical trials and critical evaluation of empiric magnesium replacement strategies are needed. It also notes that patients at risk of magnesium deficiency, with typical biochemical findings or clinical symptoms, should be considered for treatment even if serum magnesium is within the normal range.
No clinical trial has tested any drug specifically for familial primary hypomagnesemia beyond magnesium replacement. The evidence consists entirely of case reports describing genetic findings and the standard approach of lifelong magnesium supplementation. What is still missing is any randomised trial of alternative therapies, any attempt to stratify patients by specific TRPM6 mutation type, and any funding for a formal clinical study of this rare disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Intensive Care · 2018 · 198 citations · open access
Hypomagnesemia in critically ill patients
AbstractBACKGROUND: Magnesium (Mg) is essential for life and plays a crucial role in several biochemical and physiological processes in the human body. Hypomagnesemia is common in all hospitalized patients, especially in critically ill patients with coexisting electrolyte abnormalities. Hypomagnesemia may cause severe and potential fatal complications if not timely diagnosed and properly treated, and associate with increased mortality. MAIN BODY: Mg deficiency in critically ill patients is mainly caused by gastrointestinal and/or renal disorders and may lead to secondary hypokalemia and hypocalcemia, and severe neuromuscular and cardiovascular clinical manifestations. Because of the physical distribution of Mg, there are no readily or easy methods to assess Mg status. However, serum Mg and the Mg tolerance test are most widely used. There are limited studies to guide intermittent therapy of Mg deficiency in critically ill patients, but some empirical guidelines exist. Further clinical trials and critical evaluation of empiric Mg replacement strategies is needed. CONCLUSION: Patients at risk of Mg deficiency, with typical biochemical findings or clinical symptoms of hypomagnesemia, should be considered for treatment even with serum Mg within the normal range.
Case Report: Investigation and molecular genetic diagnosis of familial hypomagnesaemia: a case report
Abstract<ns4:p> Genetic mutations causing familial hypomagnesaemia syndromes are well-recognised. Affected patients can present with severe symptoms of hypomagnesaemia, such as seizures or cardiac arrhythmia. We report an affected child, from a consanguineous family, who presented in the first weeks of life with seizures secondary to hypomagnesaemia, without other associated clinical features. We performed whole exome sequencing in the affected child and segregation analysis within the family, which revealed a novel homozygous missense mutation in <ns4:italic>TRPM6</ns4:italic> , which was confirmed as a heterozygous allele in both parents and two younger siblings who had transient hypomagnesaemia. Using <ns4:italic>in silico</ns4:italic> modelling, we provide evidence that the missense variant p.(K1098E) in <ns4:italic>TRPM6</ns4:italic> is pathogenic, as it disrupts stabilising TRP domain interactions. Management of familial hypomagnesaemia relies on prompt recognition, early magnesium replacement and lifelong monitoring. </ns4:p>
Case Report: Investigation and molecular genetic diagnosis of familial hypomagnesaemia
Abstract<ns4:p> Genetic mutations causing familial hypomagnesaemia syndromes are well-recognised. Affected patients can present with severe symptoms of hypomagnesaemia, such as seizures or cardiac arrhythmia. We report an affected child, from a consanguineous family, who presented in the first weeks of life with seizures secondary to hypomagnesaemia, without other associated clinical features. We performed whole exome sequencing in the affected child and segregation analysis within the family, which revealed a novel homozygous missense mutation in <ns4:italic>TRPM6</ns4:italic> , which was confirmed as a heterozygous allele in both parents and two younger siblings who had transient hypomagnesaemia. Using <ns4:italic>in silico</ns4:italic> modelling, we provide evidence that the missense variant p.(K1098E) in <ns4:italic>TRPM6</ns4:italic> is pathogenic, as it disrupts stabilising TRP domain interactions. Management of familial hypomagnesaemia relies on prompt recognition, early magnesium replacement and lifelong monitoring. </ns4:p>
Portuguese Journal of Nephrology & Hypertension · 2023 · 0 citations · open access
A Rare Cause of Seizures: Hypomagnesemia Type 1
AbstractHypomagnesemia type I is a rare autosomal recessive disorder characterized by severe hypomagnesemia, often accompanied by hypocalcemia.This disease is caused by mutations in the TRPM6 gene (which encodes the respective channel), leading to reduced intestinal absorption of magnesium and increased renal excretion due to a defect in reabsorption in the distal convoluted tubule.It usually manifests itself in the first months of life, with symptoms of neuromuscular hyperexcitability and seizures, refractory to antiepileptic therapy.Treatment consists of administering high doses of magnesium throughout life.Here, we report a case of hypomagnesemia type I with a novel pathogenic variant of TRPM6 in a 5-month-old girl who developed refractory seizures due to hypomagnesemia.
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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