DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lysinuric protein intolerance — 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 moduleLysinuric protein intolerance 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 lysinuric protein intolerance 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
solute carrier family 7 member 7 (SLC7A7) — SLC7A7 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 glndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9I1Z · 3.45 Å · ligand GLUTAMINE (GLN). Experimental structure, not a prediction.
What the evidence adds up to
Lysinuric protein intolerance is an inherited aminoaciduria caused by mutations in the SLC7A7 gene, which encodes the y+LAT-1 protein. The condition results in defective cationic amino acid transport at the basolateral membrane of epithelial cells in the intestine and kidney. Symptoms typically begin after weaning with refusal of feeding, vomiting, and failure to thrive. Hepatosplenomegaly, haematological anomalies, and neurological involvement including hyperammonemic coma are recurrent features. Two major complications, pulmonary alveolar proteinosis and renal disease, are increasingly observed. Osteopenia is a nearly constant complication but has not been emphasised as a major feature. There is extreme variability in clinical presentation even within individual families, frequently leading to misdiagnosis or delayed diagnosis.
By 2011, approximately 50 different mutations had been identified in the SLC7A7 gene in a group of 142 patients from 110 independent families. A genuine founder effect mutation has been demonstrated only in Finland, where LPI patients share the same homozygous mutation, c.895-2A>T. No genotype-phenotype correlation could be established. The biochemical diagnosis relies on urine amino acids showing markedly elevated excretion of lysine and other dibasic amino acids despite low plasma levels of lysine, ornithine, and arginine, but the diagnosis can be uncertain and requires confirmation by DNA testing.
Therapy requires a low protein diet, low-dose citrulline supplementation, nitrogen-scavenging compounds to prevent hyperammonemia, and lysine and carnitine supplements. Supportive therapy is available for most complications, with bronchoalveolar lavage being necessary for alveolar proteinosis. The elucidation of SLC7A7 function is still needed to understand precise disease mechanisms and develop more specific and effective therapies.
What is still missing is a clear understanding of the disease mechanisms at the biochemical level, which would require further basic research funding. No clinical trial data for any targeted therapy are reported in these abstracts. Patient stratification remains impossible because no genotype-phenotype correlation has been found, and the extreme variability in presentation makes trial design difficult.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part C Seminars in Medical Genetics · 2011 · 123 citations
Lysinuric protein intolerance: Reviewing concepts on a multisystem disease
AbstractLysinuric protein intolerance (LPI) is an inherited aminoaciduria caused by defective cationic amino acid transport at the basolateral membrane of epithelial cells in intestine and kidney. LPI is caused by mutations in the SLC7A7 gene, which encodes the y(+)LAT-1 protein, the catalytic light chain subunit of a complex belonging to the heterodimeric amino acid transporter family. LPI was initially described in Finland, but has worldwide distribution. Typically, symptoms begin after weaning with refusal of feeding, vomiting, and consequent failure to thrive. Hepatosplenomegaly, hematological anomalies, neurological involvement, including hyperammonemic coma are recurrent clinical features. Two major complications, pulmonary alveolar proteinosis and renal disease are increasingly observed in LPI patients. There is extreme variability in the clinical presentation even within individual families, frequently leading to misdiagnosis or delayed diagnosis. This condition is diagnosed by urine amino acids, showing markedly elevated excretion of lysine and other dibasic amino acids despite low plasma levels of lysine, ornithine, and arginine. The biochemical diagnosis can be uncertain, requiring confirmation by DNA testing. So far, approximately 50 different mutations have been identified in the SLC7A7 gene in a group of 142 patients from 110 independent families. No genotype-phenotype correlation could be established. Therapy requires a low protein diet, low-dose citrulline supplementation, nitrogen-scavenging compounds to prevent hyperammonemia, lysine, and carnitine supplements. Supportive therapy is available for most complications with bronchoalveolar lavage being necessary for alveolar proteinosis.
Lysinuric protein intolerance: update and extended mutation analysis of theSLC7A7 gene
AbstractLysinuric protein intolerance (LPI) is an inherited aminoaciduria caused by defective cationic amino acid (CAA) transport at the basolateral membrane of epithelial cells in the intestine and kidney. LPI is caused by mutations in the SLC7A7 gene, which encodes the y(+)LAT-1 protein, the catalytic light chain subunit of a complex belonging to the heterodimeric amino acid transporter family. Coexpression of 4F2hc (the heavy chain subunit) and y(+)LAT-1 induces y(+)L activity (CAA transport). So far a total of 43 different mutations of the SLC7A7 gene, nine of which newly reported here, have been identified in a group of 130 patients belonging to at least 98 independent families. The mutations are distributed along the entire gene and include all different types of mutations. Five polymorphisms within the SLC7A7 coding region and two variants found in the 5'UTR have been identified. A genuine founder effect mutation has been demonstrated only in Finland, where LPI patients share the same homozygous mutation, c.895-2A>T. LPI patients show extreme variability in clinical presentation, and no genotype-phenotype correlations have been defined. This phenotypic variability and the lack of a specific clinical presentation have caused various misdiagnoses. At the biochemical level, the elucidation of SLC7A7 function will be necessary to understand precise disease mechanisms and develop more specific and effective therapies. In this review, we summarize the current knowledge of SLC7A7 mutations and their role in LPI pathogenesis.
New England Journal of Medicine · 1985 · 41 citations
Lysinuric Protein Intolerance Presenting as Childhood Osteoporosis
AbstractLYSINURIC protein intolerance is an autosomal recessive defect of dibasic amino acid transport.1 , 2 Renal tubular, intestinal, and hepatocellular transport is deficient, resulting in decreased circulating dibasic amino acid levels and a lack of sufficient ornithine to support activity of ornithine transcarbamylase, an intramitochondrial urea-cycle enzyme, in the liver3 (Fig. 1). Growth retardation and signs of episodic hyperammonemia are the earliest manifestations of lysinuric protein intolerance, and seizures, mental retardation, hepatomegaly, and muscle weakness may occur later. Osteopenia is a nearly constant complication but has not been emphasized as a major feature of the disorder.5 The highest reported prevalence of lysinuric . . .
Brain fog and protein logs: unravelling encephalopathy in lysinuric protein intolerance with rare mutation and expanded phenotypic spectrum
AbstractLysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by variants in the SLC7A7 gene, leading to impaired transport of dibasic amino acids across intestinal and renal membranes. This results in postprandial hyperammonaemia due to deficiencies in lysine, arginine and ornithine, crucial substrates for the urea cycle. It commonly presents in infancy with recurrent vomiting, diarrhoea and encephalopathy. Diagnosis involves molecular genetic testing for the SLC7A7 gene variant. In this case, the rarity of the neuroimaging findings and the identification of an ultra-rare mutation contribute to the expanding clinical and genetic spectrum of LPI. Despite therapeutic advancements, the prognosis of LPI hinges on the progression of pulmonary and renal complications, underscoring the importance of comprehensive care and monitoring.
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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