DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for protein energy malnutrition — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleProtein energy malnutrition maps to a 2-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 protein energy malnutrition 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
monoglyceride lipase (MGLL) — MGLL 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 7r,9ardrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7ZPG · 1.16 Å · ligand [(7R,9aR)-7-(4-chlorophenyl)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-(2-bromanyl-3-methoxy-phenyl)methanone (JQX). Experimental structure, not a prediction.
What the evidence adds up to
Plasma proteins such as albumin, transferrin and transthyretin have been proposed as markers for protein energy malnutrition, but a 1999 review concluded that inflammatory disease and drug or hormone therapy probably account for the majority of low transthyretin levels. Albumin and other proteins may help determine increased risk of morbidity and mortality, but better markers are needed for diagnosis of protein energy malnutrition per se.
Depending on the type of pathology, protein-energy malnutrition develops in 20–50% of surgical patients directly in hospital in the early postoperative period, according to 2022 clinical practice recommendations from the Russian Federation of Anesthesiologists and Reanimatologists. Between 30% and 69% of surgical patients are already hospitalised with grade I–III protein-energy malnutrition and require mandatory nutritional support. Risk factors are present in 60–70% of hospitalised patients. A 2014 study of 201 patients admitted to a mid- to long-term stay unit in Valencia found an overall malnutrition rate of 76.6%, with severe protein energy malnutrition the most common type at 20.4%. Malnourished patients were older and presented greater functional dependence.
Protein-energy malnutrition is believed to lead to increased susceptibility to infection and impaired immunity, according to a 2010 review. Infection occurring with malnutrition is a major cause of morbidity in all age groups and is responsible for two-thirds of all deaths under five years of age in developing countries. The most consistent immune changes in protein-energy malnutrition are in cell-mediated immunity, the bactericidal function of neutrophils, the complement system, secretory immunoglobulin A, and antibody response. A 1986 review described the metabolic response to chronic undernutrition as a spectrum from decreased growth velocity in mild cases to profound distortion of body composition and functional derangements in advanced stages of the malnutrition-infection complex.
What is still missing is a validated diagnostic marker for protein energy malnutrition that is not confounded by inflammation or drug therapy. The existing evidence relies on prevalence surveys and clinical practice recommendations rather than randomised trials of specific interventions. No drug is mentioned in any of these abstracts. Patient stratification by age, functional status and comorbidity is needed to determine which patients benefit from nutritional support, and funding for such trials remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Chemistry and Laboratory Medicine (CCLM) · 1999 · 73 citations
Low Levels of Plasma Proteins: Malnutrition or Inflammation?
AbstractLevels of several plasma proteins, including albumin, transferrin, and transthyretin (prealbumin), have been proposed as markers for protein energy malnutrition. However, many other factors, especially inflammatory disease and drug or hormone therapy, affect levels of these proteins. These factors probably account for the majority of low levels of transthyretin. Levels of albumin and other proteins may be helpful in determining increased risk of morbidity and mortality, but better markers are needed for diagnosis of protein energy malnutrition per se.
Annals of critical care · 2022 · 29 citations · open access
Perioperative nutritional support. Clinical practice recommendations of the national “Federation of Anesthesiologists and Reanimatologists”
AbstractNumerous publications show that, depending on the type of pathology, protein-energy malnutrition develops in 20– 50 % of surgical patients directly in the hospital in the early postoperative period. Rather a great number of patients with surgical diseases are already hospitalized with varying degrees of malnutrition. From 30 % to 69 % of patients are admitted to the hospital with I–III grade of protein-energy malnutrition and require mandatory nutritional support. Risk factors for protein-energy malnutrition development are determined in 60–70 % of hospitalized patients. This clinical practice recommendations present the basic principles of nutritional support in the perioperative period.
MAKARA of Science Series · 2010 · 13 citations · open access
EFFECTS OF PROTEIN-ENERGY MALNUTRITION ON THE IMMUNE SYSTEM
AbstractProtein-Energy Malnutrition (PEM) is believed to lead to an increased susceptibility to infection, or cause impaired immunity. Infection, occurring with malnutrition, is a major cause of morbidity in all age groups and is responsible for two-thirds of all death under 5 yr of age in developing countries. Many cells of the immune system are known to depend for their function on metabolic pathways that employ various nutrients as critical factors. The most consistent changes in immune competence in PEM are in cell-mediated immunity, the bactericidal function of neutrophils, the complement system, the secretory immunoglobin A, and antibody response. Keywords: protein-energy malnutrition, immune system, cell mediated immunity, amino acid deficiency, antibody responses Introduction
Journal of the American College of Nutrition · 1986 · 11 citations
Metabolic adaptation in protein-energy malnutrition.
AbstractThe metabolic response to chronic undernutrition covers a wide spectrum that ranges from decreased growth velocity in mild cases to profound distortion of body silhouette and composition and functional derangements in advanced stages of the protein-energy malnutrition-infection complex. A wide gamut of molecular, enzymatic, and hormonal processes assure a temporary availability of endogenous nutrients and the maintenance of vital functions.
[Prevalence of malnutrition in a mid-long term stay unit].
AbstractINTRODUCTION: Malnutrition is a common health problem, especially in hospitalized patients, where it's associated with longer hospital stays and higher rates of morbidity and mortality. Furthermore, current scientific advances and life expectancy increase, have produced a progressive increase of mid- to long-term stay units (UMLE). AIMS: To determinate the prevalence of malnutrition on admission to a mid- to long-term stay unit, using MNA and VGS and to analyze the possible factors/clinical features associated with malnutrition and its consequences. METHODS: Descriptive and transversal study conducted with 201 patients admitted consecutively for 12 months in an Universitary Hospital mid- to long-term stay unit (Valencia). Clinical, anthropometric, biochemical and nutritional history data were registered, as well as Charlson comorbidity scale, Pfeiffer cognitive scale, Barthel functional scale and presence of edema, ascitis and pressure ulcers. Nutritional status was evaluated in the first 24-72 hours of admission using MNA and VGS. Dysphagia was evaluated using EAT-10 and MECV-V questionnaires. RESULTS: The overall rate of malnutrition was 76,6%, being severe protein energy malnutrition the most common type (20,4%). Malnourished patients were older (p=0,002), presented greater dependence (p.
Malnutrition Protein-Calorie Malnutrition Robert E. Olson
AbstractMalnutrition Get access Protein-Calorie Malnutrition (Nutrition Foundation Monograph Series), edited by Olson Robert E.. Academic Press, Inc., New York, 1975, 467 p., illus., $29.50 (74-5702). Reva T. Frankle Reva T. Frankle Department of Community Medicine, Mt. Sinai School of Medicine-CUNY and Program in Nutrition, Teachers College, Columbia University, New York, NY 10027 Search for other works by this author on: Oxford Academic Google Scholar BioScience, Volume 25, Issue 8, August 1975, Page 522, https://doi.org/10.2307/1296971 Published: 01 August 1975
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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