DeCure for Hyperpigmentation with or without hypopigmentation, familial progressive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperpigmentation with or without hypopigmentation, familial progressive — 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 moduleHyperpigmentation with or without hypopigmentation, familial progressive 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 hyperpigmentation with or without hypopigmentation, familial progressive 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
KIT ligand (KITLG) — KITLG 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 1SCF · 2.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Familial progressive hyperpigmentation with or without hypopigmentation (FPHH) is an autosomal dominant disorder. A 2024 case report describes a patient with a novel KITLG mutation (Ser78Leu) who presented with multiple hypopigmented macules and striae along the lines of Blaschko. Digital polymerase chain reaction of DNA from skin and blood tissues showed a copy-neutral loss of heterozygosity at the KITLG locus only in the hypopigmented macule, suggesting revertant mosaicism as the cause. Café-au-lait spots in the same patient did not follow Blaschko’s lines and could superimpose on the hypopigmented striae, indicating a distinct pathogenesis.
A 2016 study of an 11-year-old boy with hyperpigmentation since birth found that affected members of his family shared a mutation in the c-KIT gene. All had progressive hyperpigmentation, and some also had gastrointestinal stromal tumours and mastocytoma. The authors concluded that molecular analysis of c-KIT should be considered when familial progressive hyperpigmentation presents with systemic involvement.
A 2012 report describes a two-year-old Chinese girl with diffuse hyper- and hypopigmented lesions, longitudinal melanonychia in both thumbs, and infantile seizures, but without any lentigines. This was presented as a variant case of FPHH. A 2011 article notes that familial progressive hyperpigmentation was first described in 1971 and is characterised by gradual, progressive, diffuse, generalised skin hyperpigmentation starting around birth, with no systemic involvement mentioned in that early description.
No drug treatment is mentioned in any of these abstracts. What is missing is any clinical trial testing a therapy for FPHH, any patient stratification by specific KITLG or c-KIT mutation, and any funding for such work. The genetic mechanisms are becoming clearer, but no intervention has been studied.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Indian Journal of Dermatology Venereology and Leprology · 2012 · 22 citations · open access
Familial progressive hypo- and hyperpigmentation: A variant case
AbstractFamilial progressive hyper- and hypopigmentation (FPHH) is characterized by diffuse hyperpigmentation with variable intensity. Cafe'-au-lait macules and larger hypopigmented ash-leaf macules are also present. Herein, we reported a variant case of FPHH. The patient was a two-year-old Chinese girl showing diffuse hyper- and hypopigmented lesions, longitudinal melanonychia in both thumbs, and infantile seizures, without any lentigines.
Familial Progressive Hyperpigmentation, Cutaneous Mastocytosis, and Gastrointestinal Stromal Tumor as Clinical Manifestations of Mutations in the c‐<scp>KIT</scp> Receptor Gene
AbstractBACKGROUND: Familial progressive hyperpigmentation (FPH) is an autosomal dominant disorder characterized by the appearance of hyperpigmented patches on the skin from early infancy that increase in size and number with age. METHODS: We report the clinical and molecular studies of an 11-year-old boy who had areas of hyperpigmentation since birth that had spread across his body as irregular hyperpigmented macules and papules, and include relevant history in family members. RESULTS: Affected members of his family shared a mutation in the c-KIT gene. All had progressive hyperpigmentation, in some cases accompanied by gastrointestinal stromal tumors and mastocytoma. There have been few reports of familial progressive hyperpigmentation together with systemic manifestations. CONCLUSIONS: Molecular analysis of c-KIT should be considered in the presence of FPH with systemic involvement.
European Journal of Dermatology · 2011 · 1 citations
A variant case of familial progressive hyperpigmentation
Abstractejd.2011.1374 Auteur(s) : Ru-zhi Zhang1, Wen-yuan Zhu2 [email protected] 1 Department of Dermatology, First Affiliated Hospital Bengbu Medical College, Anhui 233004, China 2 Department of Dermatology, First Affiliated Hospital Nanjing Medical University, Nanjing 210029, China Familial progressive hyperpigmentation (FPH), first described by Chernosky et al. [1] in 1971, is characterized by a gradual, progressive, diffuse, generalized skin hyperpigmentation starting around birth, with no systemic [...]
A case of familial progressive hyperpigmentation with or without hypopigmentation presenting with hypopigmented striae along the lines of Blaschko
AbstractFamilial progressive hyperpigmentation with or without hypopigmentation (FPHH) is an autosomal dominant disorder characterized by widespread skin hyperpigmentation, café-au-lait spots, and hypopigmented circular macules, resulting from KITLG variants. KITLG, expressed by keratinocytes, binds to KIT on melanocytes, stimulating melanogenesis. Disturbances in the KITLG-KIT interaction result in diffuse hyperpigmentation in FPHH. However, the mechanisms behind hypopigmented macule formation remain unclear. This report presents a unique FPHH case in a patient with a novel KITLG mutation (Ser78Leu). Notably, the patient showed multiple hypopigmented macules and striae along the lines of Blaschko. Digital polymerase chain reaction analysis of the DNA from skin and blood tissues indicated a copy-neutral loss of heterozygosity at the KITLG locus, only in the hypopigmented macule. These findings suggest that the hypopigmented macules might result from revertant mosaicism. Conversely, café-au-lait spots do not follow the lines of Blaschko and can superimpose on the hypopigmented striae, indicating a distinct pathogenesis. This case contributes to the understanding of the genetic mechanisms in FPHH.
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.
