DeCure for CIDEC-related familial partial lipodystrophy
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for CIDEC-related familial partial lipodystrophy — 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 moduleCIDEC-related familial partial lipodystrophy 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 cidec-related familial partial lipodystrophy 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.
What the evidence adds up to
A mother and daughter with an unusual familial partial lipodystrophy had atrophy of fat in the face, chest, and limbs, with abdominal obesity from intraabdominal fat. The mother had severe insulin resistance and impaired glucose tolerance; the daughter had normal glucose tolerance and normal insulin sensitivity. Both had metabolic rates about 30% above normal, with normal thyroid function and plasma lipids.
An 18-year-old Hispanic female with familial partial lipodystrophy, hirsutism, acanthosis nigricans, and marked insulin resistance was found to have an extremely rare homozygous variant in CIDEC (p.Ser75Ile) and a novel homozygous variant in WRN (p.Leu619Arg). She developed invasive papillary thyroid carcinoma at age 17. The authors note that biallelic CIDEC variant is associated with the FPL phenotype, and that co-occurrence of FPLD5 with thyroid cancer, a feature of Werner syndrome, is extremely rare. They recommend surveillance for metabolic complications of FPLD5 and for WRN-associated neoplasms and premature aging.
A 34-year-old female with parental consanguinity presented with cushingoid features, fat accumulation in the upper body, and markedly reduced subcutaneous fat in the extremities and breasts. Acanthosis nigricans was present. Low-dose dexamethasone testing excluded Cushing’s syndrome. Oral glucose tolerance test indicated insulin resistance; triglycerides were elevated, leptin was normal. Whole-body DXA showed reduced fat mass in the limbs with central fat accumulation. FibroScan revealed advanced hepatic steatosis (S3) without fibrosis. Genetic analysis identified a homozygous pathogenic LIPE gene variant (c.2182G>A), confirming autosomal recessive familial partial lipodystrophy type 6. Treatment with metformin, an SGLT-2 inhibitor, and fenofibrate was initiated. The authors note that FPLD6 presents in adulthood, is characterised by severe insulin resistance, dyslipidemia, and hepatic steatosis, and that subcutaneous lipomas may cause diagnostic confusion with multiple lipomatosis.
What is missing is any controlled trial of a drug for CIDEC-related lipodystrophy; the evidence consists of single case reports and a mother-daughter pair. No drug has been tested in a cohort of patients with this specific genotype. The field lacks funding for natural history studies, a standardised outcome measure for fat distribution or metabolic endpoints in FPLD5, and any attempt to stratify patients by the specific CIDEC variant or by co-occurring WRN mutations.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Clinical Endocrinology & Metabolism · 1995 · 11 citations
An unusual type of familial lipodystrophy.
AbstractA mother and her daughter with a novel type of familial partial lipodystrophy were studied. Both had atrophy of fat in the face, chest, and upper and lower limbs and abdominal obesity caused by intraabdominal fat accumulation. The mother had severe insulin resistance and impaired glucose tolerance, whereas the daughter had normal glucose tolerance and normal insulin sensitivity. Both had metabolic rates about 30% above normal levels, but normal thyroid function and plasma lipids.
International Journal of Molecular Sciences · 2026 · 1 citations · open access
Novel Homozygous Variants in CIDEC and WRN in a Young Female with Lipodystrophy and Thyroid Cancer
AbstractAutosomal recessive familial partial lipodystrophy type 5 (FPLD5) due to a homozygous NP_001186481.1; p.E186* CIDEC variant has previously been reported in a 19-year-old female with diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. Now, we report an 18-year-old Hispanic female who presented with FPL, along with hirsutism, acanthosis nigricans, and marked insulin resistance, and was found to have an extremely rare homozygous variant in CIDEC (NM_001199623.2:c.224G>T; NP_001186552.1; p.Ser75Ile) by whole exome sequencing. She also harbored a novel homozygous variant in WRN (NM_000553.4:c.1856T>G; NP_000544; p.Leu619Arg). Both serine 75 of the CIDEC protein and leucine 619 of the WRN protein were well conserved across species. She developed an invasive papillary thyroid carcinoma at the age of 17 years. Our report confirms the previously reported association of the biallelic CIDEC variant with the FPL phenotype and also highlights the extremely rare possibility of co-occurrence of FPLD5 with thyroid cancer, a clinical feature of Werner syndrome. Thus, our patient may not only need surveillance for the metabolic complications of FPLD5, such as diabetes, hypertriglyceridemia, and hepatic steatosis, but also for WRN-associated neoplasms and features of premature aging.
AbstractAbstract Introduction Lipodystrophy is a rare and heterogeneous disorder characterized by selective loss or abnormal redistribution of adipose tissue, leading to metabolic complications such as insulin resistance, diabetes mellitus, hepatic steatosis, and dyslipidemia. Lipodystrophy is divided into 4 main groups: congenital generalized lipodystrophy (CGL), familial partial lipodystrophy (FPLD), acquired generalized lipodystrophy (AGL), and acquired partial lipodystrophy (APL). FPLD is caused by mutations is genes regulating adipocyte function and lipid metabolism, with six subtypes identified to date. Among these, type 6 (FPLD6) results from inactivating mutation in the LIPE gene, which encodes hormone-sensitive lipase (HSL). Here, we present a very rare case of autosomal recessive familial partial lipodystrophy type 6. Clinical Case A 34-year-old female was referred for evaluation of suspected Cushing’s syndrome. She was receiving hormone replacement therapy for primary ovarian insufficiency and had no other known medical conditions. She had gestational diabetes during her second pregnancy, managed with diet alone. Over three years she gained 29 kg (BMI 35.2 kg/m²). Family history revealed parental consanguinity. Physical examination revealed characteristic cushingoid features including a prominent buffalo hump, supraclavicular fat pads, and centripetal obesity. She had fat accumulation in the upper body while subcutaneous fat was markedly reduced in the extremities and breasts (Figure 1). Acanthosis nigricans was noted in the axillary and cervical regions. Additionally, she had undergone a cosmetic liposuction procedure targeting the deltoid and occipital regions. Low-dose dexamethasone testing excluded Cushing’s syndrome. Oral glucose tolerance test indicated insulin resistance; triglycerides were elevated, while leptin was normal. Laboratory results are summarized in Table 1. Whole-body DXA demonstrated markedly reduced fat mass in the upper and lower extremities, with central fat accumulation. This distribution was compatible with partial lipodystrophy. FibroScan revealed advanced hepatic steatosis (S3) without fibrosis (F0), consistent with nonalcoholic fatty liver disease (NAFLD). Genetic analysis identified a homozygous pathogenic LIPE gene variant (c.2182G>A), confirming the diagnosis of autosomal recessive familial partial lipodystrophy type 6. Treatment with metformin, SGLT-2 inhibitor, and fenofibrate was initiated, alongside lifestyle modification and genetic counseling. Conclusion FPLD6 is a very rare subtype of familial partial lipodystrophy. Unlike other subtypes, it is caused by LIPE mutations leading to defective lipolysis, and typically presents in adulthood rather than early life. It is further characterized by severe insulin resistance, dyslipidemia, and hepatic steatosis. In addition, the presence of subcutaneous lipomas distinguishes FPLD6 from other many forms and may lead to diagnostic confusion with multiple lipomatosis.Figure 1:a.Sagittal magnetic resonance imaging (MRI) of the neck and cervical spine region demonstrating abnormal fat distribution consistent with partial lipodystrophy b.Dual-energy X-ray absorptiometry (DEXA) scan demonstrating body composition c.Posterior view of the trunk showing loss of peripheral fat and abnormal fat deposition in the upper body Table 1:Biochemical parameters of the patientIR: insulin resistance
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.
