DeCure for Systemic primary carnitine deficiency disease
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for systemic primary carnitine deficiency disease — 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 moduleSystemic primary carnitine deficiency disease 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 systemic primary carnitine deficiency disease 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 22 member 5 (SLC22A5) — SLC22A5 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 152drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9PDQ · 2.72 Å · ligand CARNITINE (152). Experimental structure, not a prediction.
What the evidence adds up to
Carnitine was approved by the US Food and Drug Administration in 1985 for treatment of primary carnitine deficiency, and in 1992 for secondary carnitine deficiency. A 2016 historical perspective states that carnitine treatment of inborn errors of metabolism is now a safe and integral part of many treatment protocols. The same review notes that there is still a lack of data from randomised clinical trials, even on the use of carnitine in inborn errors of metabolism, and that ethical issues may be a contributing factor.
A 2015 retrospective study evaluated carnitine and acylcarnitine profiles in 144 very-low-birth-weight newborns, of whom 73 were appropriate for gestational age and 71 were small for gestational age. Carnitine deficiency, defined as free carnitine below 40 µmol/L and free-to-total carnitine ratio below 0.7, was observed in both groups throughout the first five weeks of life. The maximum free carnitine reached was 36.05 µmol/L in the appropriate-for-gestational-age group and 32.24 µmol/L in the small-for-gestational-age group. Contrary to expectation, small-for-gestational-age infants had higher total carnitine, free carnitine, and total acylcarnitines during the first two weeks, with a significant difference for total acylcarnitines on days three to five. Birth weight restriction was not associated with greater carnitine deficiency in this study.
A 2022 structured review collected individual case data on clinical characteristics, genetic features, and carnitine measurements at diagnosis for primary carnitine deficiency. The data sheets contain reported results from additional testing extracted from published records. The review does not provide summary statistics or effect estimates.
What remains missing are data from randomised controlled trials that could establish the magnitude of benefit from carnitine supplementation in primary carnitine deficiency, particularly for clinical outcomes such as survival or cardiomyopathy resolution. The existing evidence is limited to observational case series and physiological measurements in preterm infants, with no controlled comparison of treated versus untreated patients. Adequate trial design and patient stratification by genotype or residual transporter function have not been performed.
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 Nutrition and Metabolism · 2016 · 20 citations · open access
Historical Perspective on Clinical Trials of Carnitine in Children and Adults
AbstractThe metabolic roles of carnitine have been greatly clarified over the past 50 years, and it is now well established that carnitine is a key player in mitochondrial generation of energy and metabolism of acetyl coenzyme A. A therapeutic role for carnitine in treatment of nutritional deficiencies in infants and children was first demonstrated in 1958, and since that time it has been used to treat a number of inborn errors of metabolism. Carnitine was approved by the US Food and Drug Administration in 1985 for treatment of 'primary carnitine deficiency', and later in 1992 for treatment of 'secondary carnitine deficiency', a definition that included the majority of relevant metabolic disorders associated with low or abnormal plasma carnitine levels. Today, carnitine treatment of inborn errors of metabolism is a safe and integral part of many treatment protocols, and a growing interest in carnitine has resulted in greater recognition of many causes of carnitine depletion. Notwithstanding, there is still a lack of data from randomized clinical trials, even on the use of carnitine in inborn errors of metabolism, although ethical issues may be a contributing factor in this regard.
The Journal of Maternal-Fetal & Neonatal Medicine · 2015 · 17 citations
Evaluation of carnitine deficit in very low birth weight preterm newborns small for their gestational age
AbstractOBJECTIVE: To verify whether small-for-gestational-age (SGA) preterm newborns represent a special risk group for carnitine deficiency. Secondary outcome includes assessment of longitudinal differences of total carnitine (TC), free carnitine (FC) and acylcarnitines between SGA and appropriate-for-gestational-age (AGA). METHODS: A retrospective study to evaluate carnitine and acylcarnitines profile on 144 very-low-birth weight newborns (VLBW), classified as AGA (n = 73) and SGA (n = 71), was performed by tandem mass spectrometry, during their first 5 weeks of life. Carnitine deficiency was defined as FC <40 µmol/L and FC/TC <0.7. RESULTS: Carnitine deficiency was observed in the two study groups throughout the monitoring period (maximum FC: 36.05 µmol/L in AGA and 32.24 µmol/L in SGA). FC/TC remains under 0.7 in both with progressive improvement. Unlike expected, a comparatively higher value of TC, FC and total acylcarnitines (tAC) was found in SGA during the first 2 weeks, with significant relevance on day 3-5, especially for tAC (p < 0.001). The only acylcarnitine with persistently lower value in SGA is C5 (p < 0.05 in first 2 weeks). CONCLUSIONS: A carnitine deficiency was demonstrated in all VLBW. Although birth weight restriction has been suggested as a risk factor for impaired carnitine status, in our study, SGA was not related with higher carnitine deficiency.
The Tohoku Journal of Experimental Medicine · 1994 · 5 citations · open access
A Preterm Infant with Secondary Carnitine Deficiency due to MCT Formula. Effective Treatment of L-Carnitine.
AbstractISHIDA, A., GOTO, A., TAKAHASHI, Y., NAKAJIMA, W., ARAI, H., TAZAWA, Y. and TAKADA, G. A Preterm Infant with Secondary Carnitine Deficiency due to MCT Formula-Effective Treatment of L-Carnitine-. Tohoku J. Exp. Med., 1994, 172 (1), 59-64-We report a preterm infant who was prescribed an MCT formula and subsequently developed carnitine deficiency with liver dysfunction and an elevation of serum CK level. A male infant who had been born at 24 weeks' gestation with birth weight 799g, was fed with an MCT formula containing 76.8% of all kinds of lipids, because of his steatorrhea after the 30th day. On the 100th day, he was noted hepatomegaly and elevation of serum levels of AST, ALT and CK. The needle biopsy of the liver indicated the existence of the liver damage. He showed low serum carnitine with high urinary loss of acylcarnitine and dicarboxylic aciduria. Administration of L-carnitine was an effective treatment. The carnitine deficiency might be exaggerated by an increased urinary loss of acylcarnitine. We should be cautious of the risk of carnitine deficiency in preterm infants during prolonged use of MCT formula.
Universiteit van Amsterdam · 2022 · 1 citations · open access
Clinical characteristics PCD
AbstractRaw data of a structured review, aiming to evaluate clinical characteristics of primary carnitine deficiency (PCD). The data sheet (Clinical charactaristics PCD.csv) contains individual case data on publication information, diagnosis, genetic characteristics and symptoms.The data sheet (Carnitine measurement diagnosis.csv) contains the results of carnitine measurements at diagnosis of individual cases. <br>The data sheet (Additional testing.xlsx) contains the reported results from additional testing extracted from the published records.
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.
