DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypokalemic periodic paralysis — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypokalemic periodic paralysis maps to a 6-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 hypokalemic 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
carbonic anhydrase 2 (CA2) — CA2 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 hydroxymercurydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3K34 · 0.9 Å · ligand 4-(HYDROXYMERCURY)BENZOIC ACID (HGB). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 Cochrane review identified three randomised or quasi-randomised trials for periodic paralysis. In the largest study, 34 of 42 participants with hypokalemic periodic paralysis completed both phases of a dichlorphenamide versus placebo crossover. For those 34, the mean improvement in attack rate and severity-weighted attack rate on dichlorphenamide relative to placebo was statistically significant (P = 0.02 and P = 0.01 respectively). Fifteen participants preferred dichlorphenamide, three preferred placebo, and six preferred their baseline medication. In the same study, 16 of 31 participants with hyperkalemic periodic paralysis had attack rate data for both phases; mean improvement in attack rate and severity-weighted attack rate on dichlorphenamide was also significant (P = 0.006 and P = 0.02). Fifteen preferred dichlorphenamide, one placebo, and five their baseline medication. Two smaller studies provided some evidence that acetazolamide improved muscle strength in eight participants with hypokalemic periodic paralysis, and that pinacidil improved muscle strength in two of four participants with hypokalemic periodic paralysis. The review authors concluded that evidence was insufficient to provide full treatment guidelines.
A 2018 observational study of patients presenting with hypokalemic paresis in India found that only 19% of the cohort had hypokalemic periodic paralysis. Probable Gitelman syndrome accounted for 28%, distal renal tubular acidosis for 22%, and probable Bartter syndrome for 20%. The study authors argued that the term "periodic" should not be used in cases of recurrent hypokalemic paralysis without thorough evaluation to identify the underlying cause, which carries different therapeutic and prognostic implications.
Two case reports from 2019 and 2021 describe individual young male patients who presented with sudden paralysis and were found to have hypokalemic periodic paralysis. Both patients' paralysis resolved with potassium repletion, and they were discharged without neurologic deficits. The reports emphasise that hypokalemic periodic paralysis is rare and must be distinguished from other causes of acute weakness, including thyrotoxic periodic paralysis, hyperkalemic periodic paralysis, and Andersen syndrome.
What is still missing: adequately powered randomised trials that stratify patients by confirmed genetic mutation rather than clinical criteria alone, and that distinguish hypokalemic periodic paralysis from the more common renal potassium-wasting disorders that mimic it. Long-term safety data for dichlorphenamide and acetazolamide in this population are limited, and no trial has compared these drugs head-to-head or tested them against potassium supplementation alone.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cochrane Database of Systematic Reviews · 2008 · 80 citations · open access
Treatment for periodic paralysis
AbstractBACKGROUND: Primary periodic paralyses are rare inherited muscle diseases characterised by episodes of flaccid weakness affecting one or more limbs, lasting several hours to several days, caused by mutations in skeletal muscle channel genes. OBJECTIVES: The objective of this review was to systematically review treatment of periodic paralyses. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (from January 1966 to July 2007), and EMBASE (from January 1980 to July 2007) and any other available international medical library sources from the University of Milan for randomised trials. SELECTION CRITERIA: We included randomised (including cross-over studies) and quasi-randomised trials in participants with primary periodic paralyses, in which any form of treatment, including physical therapy and alternative therapies, was compared to placebo or another treatment. DATA COLLECTION AND ANALYSIS: Our primary outcome measure was the change in attack severity or frequency by eight weeks from the start of treatment. Our secondary outcome measures were: change in muscle strength and mass; change in Quality of Life, using Short Form 36 (SF36) or similar; preference of treatment strategy; adverse effects at eight weeks. MAIN RESULTS: Three studies met our inclusion criteria. In one study dichlorphenamide (DCP) vs placebo was tested in two groups of participants: 42 with hypokalemic periodic paralysis (HypoPP) and 31 with hyperkalemic periodic paralysis (HyperPP), based on clinical criteria. Thirty-four of 42 participants with hypokalemic periodic paralysis completed both treatment phases. For the 34 participants having attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.02) and severity-weighted attack rate (P = 0.01) on DCP relative to placebo were statistically significant. Fifteen preferred DCP, three placebo and six their baseline medication. Twenty-four of 31 participants with hyperkalemic periodic paralysis completed both treatment phases: for the 16 participants who had attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.006) and in severity-weighted attack rate (P = 0.02) on DCP relative to placebo were significant. Fifteen preferred DCP, one placebo and five their baseline medication. Acetazolamide proved to improve muscle strength in eight participants with HypoPP in one other study and pinacidil, a potassium channel opener, also improved muscle strength in 2/4 participants with HypoPP in a third study. AUTHORS' CONCLUSIONS: The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses. The other two studies provide some evidence that either acetazolamide or pinacidil may improve muscle strength. However we still lack sufficient evidence to provide full guidelines for the treatment of people with periodic paralysis.
Archives of Internal Medicine · 1957 · 17 citations
Periodic Paralysis Associated with Hyperthyroidism
AbstractPeriodic paralysis as described by Talbott1is characterized by intermittent attacks of flaccid paralysis of the muscles of the extremities with loss of deep tendon reflexes and response to electrical stimulation of the motor nerves.2During attacks there is an associated hypokalemia which responds to treatment with potassium salts. The paralysis usually begins peripherally with more profound involvement of the extensor muscles. It may be partial, complete, localized, or generalized. There is a normal sensorium and absence of sensory changes, and the paralysis rarely involves the muscles of deglutition and phonation or the eye. Temporary bradycardia, hypotension, dilatation of the heart, and increase in the size of the paralyzed muscles have been reported. The paralysis may be present for a few hours to two or three days, and recovery proceeds in the reverse direction to the order of onset. Approximately 80%3of the reported 4504cases
Indian Journal of Endocrinology and Metabolism · 2018 · 7 citations · open access
Etiological search and epidemiological profile in patients presenting with hypokalemic paresis: An observational study
AbstractINTRODUCTION: Hypokalemia is associated with increased morbidity and at times mortality. "Hypokalemic paralysis", particularly if recurrent, has often been considered synonymous with "hypokalemic periodic paralysis (HPP)"; however, diseases such as Gitelman syndrome (GS), Bartter syndrome (BS), and renal tubular acidosis (RTA) can have identical presentation. We have tried to explore the etiological spectrum along with epidemiological and certain clinical, biochemical, and electrophysiological features in patients with hypokalemic paralysis. MATERIALS AND METHODS: as the underlying etiology of hypokalemia. We took urinary potassium >25 mmol/day as the cutoff for inappropriate renal loss of potassium in presence of hypokalemia. Serum and urinary osmolality along with arterial blood gas analysis were performed in all patients with renal loss of potassium. Serum and urinary sodium, potassium, calcium, magnesium, chloride, and creatinine were measured in normotensive patients with metabolic alkalosis. Hypertensive patients were evaluated with plasma aldosterone and renin activity. RESULTS: Probable GS topped the list involving 28% individuals of the entire cohort while probable BS, distal RTA, and HPP were diagnosed in 20%, 22%, and 19% cases, respectively. Rural tribal population (61%) and age group of 30-40 years suffered the most (48%) with concentration of cases in hot and humid summer months. CONCLUSIONS: We suggest that patients with hypokalemic paresis should be evaluated thoroughly to unmask the underlying etiology that may have a different therapeutic and prognostic connotations and not to use the term "periodic" in cases of recurrent hypokalemic paralysis.
A Case of Hypokalemic Periodic Paralysis in a Young Athlete
AbstractHypokalemic periodic paralysis (HPP) is one of the group muscle disorders that can cause sudden onset paresis or paralysis. It is a quite rare, yet, potentially life-threatening condition that, if appropriately and promptly diagnosed and treated, can be completely reversed. Other forms of periodic paralysis include thyrotoxic periodic paralysis, hyperkalemic periodic paralysis, and Anderson syndrome. We are presenting a case of a young male who presented to the emergency department (ED) with sudden paralysis to shed light on such a diagnosis and on other differential diagnoses.
Z H Sikder Women’s Medical College Journal · 2019 · 1 citations · open access
Hypokalemic periodic paralysis: a case report
AbstractHypokalemic periodic paralysis (HKPP) is a rare genetic disorder with autosomal dominant inheritance and characterized by recurrent attacks of skeletal muscle weakness with associated hypokalemia which is precipitated by stress, cold, carbohydrate load, infection, glucose infusion, hypothermia, metabolic alkalosis, anesthesia and steroids. Hypokalemic Periodic Paralysis is one form of Periodic Paralysis, a rare group of disorders that can cause of sudden onset weakness. A case of a 29 year old male is presented here. The patient presented with sudden onset paralysis of his extremities. Laboratory evaluation revealed a markedly low potassium level. The patient’s paralysis resolved upon repletion of his low potassium and he was discharged with no neurologic deficits. Although rare, Periodic Paralysis must differentiated from other causes of weakness and paralysis so that the proper treatment can be initiated quickly.
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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