DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperkalemic periodic paralysis — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHyperkalemic periodic paralysis maps to a 3-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 hyperkalemic periodic paralysis 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
sodium voltage-gated channel alpha subunit 4 (SCN4A) — SCN4A 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 2~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6AGF · 3.2 Å · ligand [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate (6OU). Experimental structure, not a prediction.
What the evidence adds up to
Hyperkalaemic periodic paralysis is a rare disorder, and the evidence for its management comes from small case series and physiological studies, not from controlled trials. A 1992 report described anaesthetic management in four affected members of one family; three had experienced paralytic episodes after previous anaesthesia, but complications were avoided in the described procedures by depleting potassium before surgery, preventing carbohydrate depletion, avoiding potassium-releasing anaesthetic drugs, and maintaining normothermia. The authors stated they had no evidence of abnormal sensitivity to nondepolarising neuromuscular relaxants. A 2023 report compared two perioperative courses in the same patient: the first surgery resulted in paralysis and a protracted hospitalisation, while the second, managed with optimisation of home medications including continued potassium-wasting diuretics, avoidance of depolarising neuromuscular blockers, thermoregulation, and glucose management, led to same-day discharge.
Acetazolamide has been studied in a 1974 investigation of potassium flux in red blood cells from three patients with hyperkalemic periodic paralysis. During attack-free states, potassium influx rates were normal, but they decreased during induced attacks. Twenty-four-hour administration of acetazolamide decreased resting potassium influx rates and minimised further decreases caused by attack-inducing procedures. The authors suggested that acetazolamide alters potassium exchange between intracellular and extracellular compartments in a way that protects against sudden rises in plasma potassium. A 1979 review of hypokalemic periodic paralysis, a different condition, noted that the most effective therapy for that disorder was acetazolamide, which induces a mild metabolic acidosis thought to stabilise the cell membrane against intracellular potassium shifts; this mechanism is not directly transferable to hyperkalemic periodic paralysis.
What is still missing is any randomised trial of acetazolamide or any other drug specifically for hyperkalemic periodic paralysis. The available data are limited to three patients in one flux study and anecdotal anaesthesia reports from two families. No large prospective study has defined optimal potassium targets, the best diuretic regimen, or whether acetazolamide reduces attack frequency or severity in a clinically meaningful way. Patient stratification by genotype or by presence of paramyotonia has not been tested, and funding for such trials remains 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.
Anaesthesia · 1992 · 42 citations · open access
Hyperkalaemic periodic paralysis and anaesthesia
AbstractHyperkalaemic periodic paralysis is the rarer of the two forms of potassium-associated familial paralysis. We report a family with hyperkalaemic periodic paralysis with paramyotonia and the anaesthetic management of four affected members. In three of these, paralytic episodes had been precipitated by previous anaesthesia, but this was avoided in the anaesthetics described. We conclude from our experiences that with depletion of potassium before surgery, prevention of carbohydrate depletion, avoidance of potassium-releasing anaesthetic drugs and maintenance of normothermia, patients with hyperkalaemic periodic paralysis can be anaesthetised without complications. We have no evidence that they exhibit abnormal sensitivity to nondepolarising neuromuscular relaxants.
AbstractBACKGROUND: Hyperkalemia has been described as a rare and under recognized cause of acute quadriplegia. CASE REPORT: A 52-year-old man with end-stage renal disease presented with ascending quadriplegia and dyspnea for 2 days. He had life-threatening hyperkalemia (9.0 mEq/L). His electrocardiogram showed typical features of hyperkalemia. His symptoms improved in 30 minutes and completely resolved in 5 hours after emergent treatment of hyperkalemia. He admitted eating large amounts of high potassium foods and taking ibuprofen in uncertain quantities. We reviewed 62 articles and identified 73 patients with secondary hyperkalemic paralysis. Common presentations were diminished reflexes, quadriparesis/paralysis, respiratory involvement, and sensory loss. Almost half of all patients had potassium levels higher than 9 mEq/L. Complete recovery, achieved in 89% of patients, did not correlate either with the absolute potassium level or the degree to which it was corrected. CONCLUSIONS: Hyperkalemia is a rare but treatable cause of acute flaccid paralysis that requires immediate treatment. Late diagnosis can delay appropriate treatment leading to cardiac arrhythmias and arrest.
Acetazolamide and Potassium Flux in Red Blood Cells
AbstractRates of potassium influx in red blood cells of three patients with hyperkalemic periodic paralysis were studied during attack-free states and during induced attacks of weakness. Potassium influx rates were normal when the patients were free of attacks but decreased during attacks. Twenty-four-hour administration of acetazolamide decreased resting potassium influx rates and minimized any further decreases due to the attack-inducing procedures. The data suggest that acetazolamide administration alters potassium exchange rates between intracellular and extracellular compartments in such a way as to protect from sudden upward surges in plasma potassium levels.
BMJ Case Reports · 2023 · 2 citations · open access
Hyperkalemic periodic paralysis with paramyotonia and the anaesthetic implications
AbstractHyperkalemic periodic paralysis (HyperKPP) is a rare disease with significant anaesthetic implications. We compare two perioperative courses in the same patient. The first surgery resulted in paralysis and a protracted hospitalisation, while the second surgery resulted in a same-day discharge. Various anaesthetic techniques may be used; however, clear communication surrounding optimisation both for home medications (eg, continuing potassium wasting diuretics) and avoidance of triggering medications (primarily: depolarising neuromuscular blockers), along with thermoregulation and glucose management plans, is critical and best performed early by an anaesthetic precare clinic. Our cases highlight the physiological underpinnings in managing patients with HyperKPP.
Hypokalemic Periodic Paralysis — The Syndrome and its Treatment
AbstractHypokalemic periodic paralysis (hypoKPP) is a genetically determined disease characterized by episodic decreases in serum potassium levels accompanied by muscle weakness or paralysis. A case is reported and a review of the literature presented. Current evidence suggests that the primary defect associated with hypoKPP resides either in the muscle cell membranes or in the cellular metabolism and gives rise to a conduction defect which results in muscle paralysis. A variety of drugs have been employed to correct the cellular abnormality, including supplemental potassium, diuretics, propranolol and diazoxide. To date the most effective therapy is acetazolamide, which induces a mild metabolic acidosis thought to stabilize the cellular membrane against intracellular shifts of potassium ions.
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.
