DeCure for Short chain acyl-CoA dehydrogenase deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for short chain acyl-CoA dehydrogenase deficiency — 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 moduleShort chain acyl-CoA dehydrogenase deficiency 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 short chain acyl-coa dehydrogenase deficiency 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
acyl-CoA dehydrogenase medium chain (ACADM) — ACADM 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 faddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8SGP · 2.69 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
The three abstracts provided do not address short chain acyl-CoA dehydrogenase deficiency (SCADD). They concern very long chain (VLCADD) and medium chain (MCADD) acyl-CoA dehydrogenase deficiencies. No drug repurposing data for SCADD appear in these texts.
For VLCADD, one patient with a severe neonatal presentation and cardiomyopathy had enzyme activity at 2% of control levels. Dietary management with skimmed milk, medium chain triglycerides, and L-carnitine produced a good outcome with no acute recurrence. This is a single case, not a trial.
For MCADD, newborn screening programmes report that a positive test has high predictive value, but diagnosis must be confirmed independently. Basic treatment is dietary: avoid fasting and ensure high carbohydrate intake during illness. One Chinese case report describes a 2-year-old with hepatomegaly and abnormal liver function during a common illness, diagnosed by tandem mass spectrometry and genetic analysis showing compound heterozygosity for a missense mutation and a 4-bp deletion. No drug treatment is mentioned.
What is missing for SCADD specifically: no abstracts on SCADD were provided, so there is no evidence base to discuss. For the related disorders described, there are no randomised trials, no controlled data on any drug, and no information on patient stratification or funding for SCADD research.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurosciences · 2016 · 97 citations · open access
Fatty Acid Beta-Oxidation Disorders: A Brief Review
AbstractBACKGROUND: Mitochondrial fatty acid β-oxidation disorders (FAODs) are a heterogeneous group of defects in fatty acid transport and mitochondrial β-oxidation. They are inherited as autosomal recessive disorders and have a wide range of clinical presentations. SUMMARY: The background information and case report provide important insight into mitochondrial FAODs. The article provides a wealth of information describing the scope of these disorders. KEY MESSAGES: This article presents a typical case of medium chain acyl-CoA dehydrogenase deficiency and summarizes the pathophysiology, clinical presentation, diagnosis and treatment of mitochondrial FAODs.
Archives of Disease in Childhood · 2001 · 32 citations · open access
A severe genotype with favourable outcome in very long chain acyl-CoA dehydrogenase deficiency
AbstractA patient with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is reported. He had a severe neonatal presentation and cardiomyopathy. He was found to be homozygous for a severe mutation with no residual enzyme activity. Tandem mass spectrometry on dried blood spots revealed increased long chain acylcarnitines. VLCAD enzyme activity was severely decreased to 2% of control levels. Dietary management consisted of skimmed milk supplemented with medium chain triglycerides and L-carnitine. Outcome was good and there was no acute recurrence.
Archives of Disease in Childhood · 2008 · 30 citations
Newborn screening for medium chain acyl CoA dehydrogenase deficiency
AbstractMedium chain acyl CoA dehydrogenase deficiency (MCADD) is an uncommon inborn error of fatty acid oxidation that is a preventable cause of morbidity and mortality. Newborn screening for MCADD has been introduced in many centres worldwide and in this review we outline what the clinician needs to know. In most screening programmes a positive screening test has a high predictive value, but the diagnosis should always be confirmed independently. The basic treatment is dietary: avoid fasting and ensure a high carbohydrate intake during any illness. Careful attention to detail is essential as the long term outcome is only as good as the frontline clinical management.
The effect of long-term oral L-carnitine administration on insulin sensitivity, glucose disposal, plasma concentrations of leptin and acylcarnitines, and urinary acylcarnitine excretion in warmblood horses
AbstractBACKGROUND: Insulin resistance in horses is an emerging field of interest as it is thought to be a contributing factor in the pathogenesis of many equine conditions. OBJECTIVES: The objectives of the present study were to determine the effects of long-term oral administration of L-carnitine on insulin sensitivity, glucose disposal, plasma leptin concentrations and acylcarnitine spectrum both in plasma and urine. ANIMALS AND METHODS: Six 3-year-old healthy warmblood geldings were used. In a double blind 2 × 2 Latin square design at a dosage of 100 mg/kg body weight (BW)/day for 28 days the effects of oral supplementation of L-carnitine (as fumarate) were assessed. Glucose disposal and insulin sensitivity were measured by means of the euglycemic-hyperinsulinemic clamp technique. Radioimmunoassays were used to determine plasma leptin and insulin concentrations. Electrospray tandem mass spectrometry was used to assess acylcarnitines both in plasma and urine. Statistical analysis was performed using a linear mixed-effects model and P values <0.05 were considered significant. RESULTS: Long-term L-carnitine administration did not affect insulin sensitivity. Plasma leptin and free carnitine concentrations in plasma and urine increased significantly (P = 0.047 and 0.000, respectively) following L-carnitine administration as well as short-chain acylcarnitines in plasma and urinary excretion of short- and medium-chain acylcarnitines. CONCLUSION AND CLINICAL RELEVANCE: Given the effects of oral administration of L-carnitine further clinical study is necessary in order to assess the potential beneficial effects in equine patients suffering from metabolic myopathies such as acquired multiple acyl-CoA dehydrogenase deficiency. IMPACT FOR HUMAN MEDICINE: The current study supports the treatment rationale of short-chain acyl-CoA dehydrogenase deficiency in humans with L-carnitine at an oral dosage of 100 mg/kg BW/day.
Retrograde response to mitochondrial dysfunctions associated to LOF variations in <i>FLAD1</i> exon 2: unraveling the importance of RFVT2
AbstractFlavin adenine dinucleotide (FAD) synthase (EC 2.7.7.2), encoded by human flavin adenine dinucleotide synthetase 1 (FLAD1), catalyzes the last step of the pathway converting riboflavin (Rf) into FAD. FLAD1 variations were identified as a cause of LSMFLAD (lipid storage myopathy due to FAD synthase deficiency, OMIM #255100), resembling Multiple Acyl-CoA Dehydrogenase Deficiency, sometimes treatable with high doses of Rf; no alternative therapeutic strategies are available. We describe here cell morphological and mitochondrial alterations in dermal fibroblasts derived from a LSMFLAD patient carrying a homozygous truncating FLAD1 variant (c.745C > T) in exon 2. Despite a severe decrease in FAD synthesis rate, the patient had decreased cellular levels of Rf and flavin mononucleotide and responded to Rf treatment. We hypothesized that disturbed flavin homeostasis and Rf-responsiveness could be due to a secondary impairment in the expression of the Rf transporter 2 (RFVT2), encoded by SLC52A2, in the frame of an adaptive retrograde signaling to mitochondrial dysfunction. Interestingly, an antioxidant response element (ARE) is found in the region upstream of the transcriptional start site of SLC52A2. Accordingly, we found that abnormal mitochondrial morphology and impairments in bioenergetics were accompanied by increased cellular reactive oxygen species content and mtDNA oxidative damage. Concomitantly, an active response to mitochondrial stress is suggested by increased levels of PPARγ-co-activator-1α and Peroxiredoxin III. In this scenario, the treatment with high doses of Rf might compensate for the secondary RFVT2 molecular defect, providing a molecular rationale for the Rf responsiveness in patients with loss of function variants in FLAD1 exon 2.HIGHLIGHTSFAD synthase deficiency alters mitochondrial morphology and bioenergetics;FAD synthase deficiency triggers a mitochondrial retrograde response;FAD synthase deficiency evokes nuclear signals that adapt the expression of RFVT2.
Journal of Pediatric Endocrinology and Metabolism · 2014 · 6 citations
First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China
AbstractMedium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is an autosomal recessive inborn error of mitochondrial fatty acid β-oxidation, caused by mutations in the ACADM gene. As it is the most commonly inherited disorder of the mitochondrial fatty acid oxidation in Caucasians, there are no related reports in China diagnosed by molecular genetic testing. We report here the case of a 2-year-old female patient who had hepatomegaly and abnormal liver function with a common illness, and who had been healthy before. A marked increase found in the concentration of C8-carnitine with the help of tandem mass spectrometry (MS/MS) profile, as well as the presence of hexanoylglycine and cyclohepta acyl glycinate as shown in the urinary gas chromatography/mass spectrometry (GC/MS) were suggestive of MCADD, a diagnosis that was confirmed by genetic analysis that showed compound heterozygosity for a missense mutation, c.362C>T(p.Thr121Ile), and a 4-bp deletion, c.448-453delCTGA, in the medium-chain acyl-coenzyme A dehydrogenase (MCAD) gene, also named ACADM gene. There are no related reports in China. This report broadens the phenotype and genotype of MCADD in China and underlines the difficulty of diagnosis.
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.
