DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Loeys-Dietz syndrome 4 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLoeys-Dietz syndrome 4 maps to a 1-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 loeys-dietz syndrome 4 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
transforming growth factor beta 2 (TGFB2) — TGFB2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8FXV · 2.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Loeys-Dietz syndrome is a connective tissue disorder caused by heterozygous mutations in genes encoding type I or II transforming growth factor-beta receptor, or in SMAD2, SMAD3, TGFB2, or TGFB3. The syndrome manifests with aggressive vascular pathology: aneurysms may form at a young age, have a propensity for arterial dissection, and rupture at diameters smaller than those used to dictate surgical intervention for other syndromes. Early diagnosis and rapid intervention are described as instrumental in averting catastrophic events, with serial imaging assessment by radiologists an important component of management.
In 2020 the first case of Loeys-Dietz syndrome due to biallelic SMAD3 likely pathogenic variants was reported in a 15-year-old male. He had classic features including dysmorphic facial features, significant scoliosis, pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents were each heterozygous for the likely pathogenic variant and were more mildly affected. This was the third reported case of biallelic Loeys-Dietz syndrome in the literature, indicating multiple genetic modes of inheritance.
A 2014 case report described anaesthetic management of a Loeys-Dietz syndrome type I patient who presented for laparotomy due to a suspected twisted ovarian cyst. Type I accounts for more than 75% of cases. The report did not provide survival or response rate data, nor did it test any drug intervention.
No drug treatment for Loeys-Dietz syndrome is evaluated in these abstracts. What is missing are clinical trials of any pharmacological agent, prospective data on medical management to slow aneurysm progression, and patient stratification by genotype (heterozygous versus biallelic) to guide surveillance or intervention.
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 Roentgenology · 2007 · 84 citations
Loeys-Dietz Syndrome: MDCT Angiography Findings
AbstractOBJECTIVE: Loeys-Dietz syndrome is a newly described phenotype caused by heterozygous mutations in the genes encoding type I or II transforming growth factor-beta (TGF-beta) receptor. Characterized by a unique constellation of clinical and pathologic findings, Loeys-Dietz syndrome manifests with aggressive vascular pathology. Aneurysms may form at a young age and have a propensity for arterial dissection. In addition, aneurysms rupture at diameters smaller than those used to dictate surgical intervention for other syndromes and disorders. This article presents the spectrum of arterial pathology that may be identified on MDCT angiography in patients with Loeys-Dietz syndrome. CONCLUSION: For patients with Loeys-Dietz syndrome, early diagnosis and rapid intervention are instrumental in averting catastrophic events. Serial imaging assessment by radiologists is an important component in the management of these patients.
Overexpression of Gremlin-1 in Patients with Loeys-Dietz Syndrome: Implications on Pathophysiology and Early Disease Detection
AbstractBACKGROUNDS: The Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder caused by mutations in the transforming growth factor β (TGF-β) receptors TGFBR1 or TGFBR2. Most patients with LDS develop severe aortic aneurysms resulting in early need of surgical intervention. In order to gain further insight into the pathophysiology of the disorder, we investigated circulating outgrowth endothelial cells (OEC) from the peripheral blood of LDS patients from a cohort of 23 patients including 6 patients with novel TGF-β receptor mutations. METHODS AND RESULTS: We performed gene expression profiling of OECs using microarray analysis followed by quantitative PCR for verification of gene expression. Compared to OECs of age- and sex-matched healthy controls, OECs isolated from three LDS patients displayed altered expression of several genes belonging to the TGF-β pathway, especially those affecting bone morphogenic protein (BMP) signalling including BMP2, BMP4 and BMPR1A. Gene expression of BMP antagonist Gremlin-1 (GREM1) showed the most prominent up-regulation. This increase was confirmed at the protein level by immunoblotting of LDS-OECs. In immunohistochemistry, abundant Gremlin-1 protein expression could be verified in endothelial cells as well as smooth muscle cells within the arterial media. Furthermore, Gremlin-1 plasma levels of LDS patients were significantly elevated compared to healthy control subjects. CONCLUSIONS: These findings open new avenues in the understanding of the pathogenesis of Loeys-Dietz syndrome and the development of new diagnostic serological methods for early disease detection.
American Journal of Medical Genetics Part A · 2020 · 4 citations
The first reported case of <scp>Loeys‐Dietz</scp> syndrome in a patient with biallelic <scp><i>SMAD3</i></scp> variants
AbstractLoeys-Dietz syndrome (LDS), a connective tissue disorder characterized by its vascular, skeletal, craniofacial, and cutaneous manifestations is caused by mutations in one of six genes (TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3). Until recently, all reported cases of LDS have been attributed to heterozygous pathogenic variants in these genes. Here, we report the first case of Loeys-Dietz syndrome due to SMAD3 biallelic likely pathogenic variants in a 15-year-old male with classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected. To our knowledge, this represents the first reported case of biallelic SMAD3-related Loeys-Dietz syndrome and the third case in the literature of biallelic LDS, indicating that there are multiple genetic modes of inheritance underlying this disorder.
Biomedical Journal of Scientific & Technical Research · 2018 · 1 citations · open access
Dental Approach in Individuals with Loeys-Dietz Syndrome: A Mini Review
AbstractLoeys-Dietz syndrome (LDS) is a connective tissue disease which develops due to the mutations in the genes synthesizing TFG-beta receptors. Hypertelorism, cleft palate with bifid uvula and arterial/aortic aneurysms are the 3 basic elements of the disease forming a triad. Considering oral and maxillofacial findings in individuals with Loeys-Dietz syndrome, the responsibility of dentist is very important both in diagnosis of syndrome and in treatment. In the literature, there has been no publication of a dental approach to LDS and it is expected that this publication may be a guide to dentists for the syndrome.
Journal of Evolution of Medical and Dental Sciences · 2014 · 0 citations · open access
ANAESTHETIC MANAGEMENT FOR A RARE CASE OF LOEYS - DIETZ SYNDROME FOR LAPAROTOMY
AbstractLoeys-Dietz syndrome (LDS) is an autosomally dominant connective tissue disorder characterised by vascular and skeletal manifestations. It is caused by mutations in the TGFBR1, TGFBR2, TGFB2 or SMAD3 genes. There are four types of which type I is the most common accounting for more than 75% of the cases. Here we report the anaesthetic management of a case of LDS type I who presented with abdominal pain with suspected twisted ovarian cyst for laparotomy.
Malaysian Journal of Paediatrics and Child Health · 2023 · 0 citations · open access
Aggressive Aortic Disease with Marfan-like Phenotype in Malaysian Patients with Loeys-Dietz Syndrome
AbstractLoeys- Dietz Syndrome (LDS, pronounced LOH-eez-DEETS) is a connective tissue disorder that was first described in 2005. In the past, many patients were misdiagnosed clinically as Marfan Syndrome (MFS) due to their overlapping phenotype. Distinguishing craniofacial features of LDS include hypertelorism, bifid uvula, cleft palate and absence of lens dislocation. Unlike MFS, aortic root dilatation with or without arterial tortuosity elsewhere are almost always present. Patient 1 was a 7-year- old boy, diagnosed with MFS at 4 years of age. Echocardiogram showed aortic root dilatation with no lens dislocation on eye assessment. He was initially started on β-blocker by the cardiologist, losartan was added on subsequently due to the increasing size of his aortic root diameter. Patient 2 was a 14-year-old boy, followed up for severe aortic root dilatation. He had a stormy neonatal period; diagnosed with tracheobronchomalacia, multiple joint dislocation, feeding intolerance, scoliosis and squint. He was followed up for many years as possible MFS. Genetic testing performed showed mutation at TGFBR2 gene, confirming a diagnosis of LDS in both patients. In addition to these families, another 6 families under our aortopathy clinic follow up have had their diagnosis of LDS confirmed molecularly. LDS is increasingly being described in patients with a more severe aortic disease and Marfan-like phenotype. The difference in disease severity highlights the importance of genetic testing in patients with suspected aortopathy, enabling timely implementation of therapeutic strategies.
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.
