DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intestinal hypomagnesemia 1 — 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 moduleIntestinal hypomagnesemia 1 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 intestinal hypomagnesemia 1 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
A 2016 review of mechanisms notes that new gastrointestinal and renal causes of hypomagnesemia have been documented, but it does not report any trial results or patient outcomes. A 2017 case report describes a long-term proton pump inhibitor (PPI) user with persistent severe hypomagnesemia who was dependent on weekly intravenous magnesium infusions and could not stop PPI because of severe reflux. After laparoscopic fundoplication, his magnesium levels normalised without supplementation. A 2016 retrospective review of 1000 post-Roux-en-Y gastric bypass patients on prophylactic PPI for one year found only five cases of hypomagnesemia, none clearly related to PPI use, and concluded the risk is minimal.
A 2023 case series reports four patients without diabetes who had severe refractory hypomagnesemia and were treated with SGLT2 inhibitors. Case 1 had calcineurin inhibitor-associated hypomagnesemia and was able to withdraw from high-dose oral magnesium. Cases 2 and 3 had hypomagnesemia from platinum-based chemotherapy and achieved independence from intravenous magnesium; case 4 had decreased intravenous magnesium requirements. All four showed sustainably improved serum magnesium. Withdrawal of the SGLT2 inhibitor in case 4 led to worsening serum magnesium and increased intravenous magnesium needs. The authors note this is a small uncontrolled series and call for further studies.
No randomised trial has tested any drug specifically for intestinal hypomagnesemia 1. The SGLT2 inhibitor data come from four non-diabetic patients with mixed causes of hypomagnesemia, not from a cohort with a defined genetic magnesium absorption defect. The PPI-related cases are anecdotal and the large bypass review found no PPI-driven hypomagnesemia. What is missing is a dedicated trial in patients with confirmed intestinal hypomagnesemia 1, funding for such a study, and any evidence that SGLT2 inhibitors or other drugs work in that specific genetic population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Kidney Medicine · 2023 · 25 citations · open access
SGLT2 Inhibitors in Management of Severe Hypomagnesemia in Patients Without Diabetes: A Report of 4 Cases
AbstractSodium/glucose cotransporter 2 (SGLT2) inhibitors have demonstrated a class effect in improving serum magnesium levels in patients with diabetes. Additionally, recent reports have shown their promising beneficial effects in the treatment of refractory hypomagnesemia in patients with diabetes. However, their role in treating hypomagnesemia in patients without diabetes remains unexplored. Here, we report 4 cases of severe and refractory hypomagnesemia that showed dramatic improvement after initiating SGLT2 inhibitors in patients without diabetes. Case 1 had calcineurin inhibitor-associated severe hypomagnesemia. Cases 2, 3, and 4 had refractory hypomagnesemia associated with platinum-based chemotherapy with or without gastrointestinal losses. Case 1 was able to withdraw from high-dose oral magnesium supplementation. Cases 2 and 3 achieved independence from intravenous magnesium supplementation, whereas case 4 had decreased intravenous magnesium requirements. All the cases demonstrated sustainably improved serum magnesium levels. Withdrawal of SGLT2 inhibitors in case 4 resulted in worsening serum magnesium levels and intravenous magnesium requirements. The extraglycemic benefit of this group of medications not only suggests the need for further studies to better understand the effect of SGLT2 inhibitors on magnesium homeostasis but also supports expanded use in a larger patient population.
World Journal of Gastroenterology · 2017 · 11 citations · open access
Persistent severe hypomagnesemia caused by proton pump inhibitor resolved after laparoscopic fundoplication
AbstractMagnesium deficiency can cause a variety of symptoms, including potentially life-threatening complications such as seizures, cardiac arrhythmias and secondary electrolyte disturbances. Hypomagnesemia can be a serious adverse effect to proton pump inhibitor (PPI) therapy, which is worrying due to the widespread use of PPIs. Current evidence suggest that the mechanism of PPI induced hypomagnesemia is impaired intestinal magnesium absorption. In this report, we present the case of a long-term PPI user with persistent hypomagnesemia with severe symptoms at presentation. He was unable to stop PPI treatment because of severe reflux symptoms, and was dependent on weekly intravenous magnesium infusions, until his magnesium levels finally normalized without the need for supplementation after a successful laparoscopic fundoplication.
Obesity Surgery · 2016 · 5 citations · open access
Proton Pump Inhibitor Prophylaxis After Gastric Bypass Does Not Cause Hypomagnesemia
AbstractProton pump inhibitor (PPI)-induced hypomagnesemia is currently a major topic. Patients undergoing Roux-en-Y gastric bypass are generally prescribed PPI prophylaxis after surgery. We investigated the prevalence of hypomagnesemia in our bariatric population. We reviewed the files of 1000 postoperative patients for serum magnesium level during PPI use. We found only five cases of hypomagnesemia, none of which was evidently related to PPI use. We conclude that the risk of hypomagnesemia during 1 year of prophylactic PPI use after Roux-en-Y gastric bypass (RYGB) is minimal and laboratory screening is probably not necessary.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
