DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Kindler syndrome — 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 moduleKindler syndrome 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 kindler syndrome 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
Kindler syndrome is an autosomal recessive skin disorder caused by loss-of-function mutations in the FERMT1 gene (also known as KIND1), which encodes the focal adhesion protein kindlin-1. Fewer than 100 cases had been described in the literature as of 2011. The condition presents with acral blisters in the neonatal period, trauma-induced blistering in early childhood, photosensitivity, and a progressive poikiloderma with extensive skin atrophy. Mucosal inflammation and stenosis, including colonic inflammation, are also reported. A 2025 case report from a developing country states that the syndrome can be diagnosed clinically without genetic testing.
The natural history, based on a 2011 review of 62 patients, includes an age-dependent progression and a propensity to skin cancer. Most FERMT1 mutations are predicted to cause premature termination of translation and loss of kindlin-1 function. Significant clinical variability is observed among patients. Missense and in-frame deletion mutations are associated with milder disease and later onset of complications, but genotype-phenotype correlations do not fully explain the variability. Environmental factors and unidentified modifiers are thought to play a role. Novel mutations continue to be reported: a 2005 paper described a new homozygous nonsense mutation (C468X) in an Indian child, and a 2022 paper reported the first family with a homozygous c.1676G>A variant.
No drug treatment is mentioned in any of these abstracts. There are no data on survival, response rates, or sample sizes for any therapeutic intervention. The 2011 review calls for better understanding of molecular pathogenesis to enable prevention strategies for disease complications. The 2025 case report emphasises early recognition, regular surveillance for malignancy, and a multidisciplinary approach including psychosexual health. What remains missing is any clinical trial testing a specific drug, any funded repurposing effort, and any stratification of patients by mutation type or disease stage that could guide future therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Mutation · 2011 · 133 citations · open access
Kindler syndrome: Extension of FERMT1 mutational spectrum and natural history
AbstractMutations in the FERMT1 gene (also known as KIND1), encoding the focal adhesion protein kindlin-1, underlie the Kindler syndrome (KS), an autosomal recessive skin disorder with an intriguing progressive phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. Herein we review the clinical and genetic data of 62 patients, and delineate the natural history of the disorder, for example, age at onset of symptoms, or risk of malignancy. Although most mutations are predicted to lead to premature termination of translation, and to loss of kindlin-1 function, significant clinical variability is observed among patients. There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications. Nevertheless, the clinical variability is not fully explained by genotype-phenotype correlations. Environmental factors and yet unidentified modifiers may play a role. Better understanding of the molecular pathogenesis of KS should enable the development of prevention strategies for disease complications.
Novel and Recurrent FERMT1 Gene Mutations in Kindler Syndrome
AbstractKindler syndrome (OMIM 173650) is an autosomal recessive condition characterized by skin blistering, skin atrophy, photosensitivity, colonic inflammation and mucosal stenosis. Fewer than 100 cases have been described in the literature. First reported in 1954, the molecular basis of Kindler syndrome was elucidated in 2003 with the discovery of FERMT1 (KIND1) loss-of-function mutations in affected individuals. The FERMT1 gene encodes kindlin-1 (also known as fermitin family homologue 1), a 77 kDa protein that localizes at focal adhesions, where it plays an important role in integrin signalling. In the current study, we describe five novel and three recurrent loss-of-function FERMT1 mutations in eight individuals with Kindler syndrome, and provide an overview of genotype-phenotype correlation in this disorder.
Clinical and Experimental Dermatology · 2005 · 18 citations
An Indian child with Kindler syndrome resulting from a new homozygous nonsense mutation (C468X) in the KIND1 gene
AbstractKindler syndrome is an inherited skin condition that presents with blistering followed by photosensitivity and a progressive poikiloderma. The disorder results from mutations in the KIND1 gene, encoding the protein kindlin-1, a recently characterized 677-amino acid protein involved in anchorage of the actin cytoskeleton to the extracellular matrix. We report the clinical features of an 11-year-old boy with Kindler syndrome from a consanguineous Indian family and the identification of a homozygous nonsense mutation (C468X) in exon 12 of the KIND1 gene in his genomic DNA. This mutation has not been described previously but is similar to the 17 previously published KIND1 mutations that are all predicted to lead to loss of kindlin-1 protein expression and function. The clinical features in this boy highlight the relevance of kindlin-1 in skin biology, specifically to epidermal adhesion and response to acute and chronic sun exposure. Delineation of this new pathogenic mutation in KIND1 is also useful for genetic counselling in this family and in assessing carrier status in unaffected family members.
Clinical and Experimental Dermatology · 2005 · 18 citations
Retrospective diagnosis of Kindler syndrome in a 37-year-old man.
AbstractKindler syndrome is a rare autosomal recessive disorder characterized by acral blisters in infancy and early childhood, followed by photosensitivity, progressive poikiloderma and cutaneous atrophy. Other features include webbing of the toes and fingers, palmoplantar hyperkeratosis, gingival fragility, poor dentition, and mucosal involvement in the form of urethral, anal and oesophageal stenosis. The recent finding of KIND1 mutations in Kindler syndrome facilitates early diagnosis, prophylactic measures and more precise definition of the phenotype. In the family described here, molecular diagnosis of Kindler syndrome in an infant with acral blisters led to the belated diagnosis in a severely affected relative whose condition had remained unidentified for 37 years.
Actas Dermo-Sifiliográficas · 2020 · 12 citations · open access
Síndrome de Kindler, manejo multidisciplinario
AbstractEl síndrome de Kindler es un subtipo de epidermólisis bullosa hereditaria muy rara, causada por la mutación del gen FERMT1 que codifica la proteína kindlina-1. Clínicamente, se caracteriza por la formación de ampollas inducidas por traumatismo, atrofia cutánea difusa, poiquilodermia, seudosindactilia y fotosensibilidad. En las mucosas, las manifestaciones más frecuentes incluyen conjuntivitis, ectropión, gingivitis hemorrágicas, enfermedad periodontal, pérdida prematura de dientes y colitis severa. Presentamos los 4 primeros casos con síndrome de Kindler, diagnosticados en el Instituto Nacional de Salud del Niño, Lima, Perú, con el fin de dar a conocer su particular forma de presentación y variedad de manifestaciones clínicas, enfatizando en que este hecho obligó a realizar un manejo multidisciplinario, que permitió un control adecuado de los síntomas y una notable mejoría en su calidad de vida. Kindler syndrome is a very rare form of bullous epidermolysis. It is a hereditary condition caused by a mutation in the FERMT1 gene that encodes the protein kindlin-1. It is clinically characterized by trauma-induced blistering, diffuse skin atrophy, poikiloderma, pseudosyndactyly, and photosensitivity. The most common mucosal manifestations are conjunctivitis, ectropion, hemorrhagic gingivitis, periodontal disease, premature tooth loss, and severe colitis. We present the first 4 cases of Kindler syndrome diagnosed at the Instituto Nacional de Salud del Niño in Lima, Peru. These cases highlight the unique clinical presentation and multiple manifestations of this disease and show how a multidisciplinary management approach kept symptoms under control and significantly improved patient quality of life.
Clinical and Experimental Dermatology · 2022 · 1 citations
First report of the c.1676G>A homozygous variant in a family with Kindler syndrome
AbstractKindler syndrome (KS) was first described by Theresa Kindler in 1954, and since then > 60 pathogenic variants have been identified in the FERMT1 gene for KS. Most FERMT1 variants associated with KS are null variants. We present the case of a child with poikilodermic changes on the forehead and cheeks, who was found to have a homozygous c.1676G>A mutation. To our knowledge, this is the first report of this mutation in a family with KS.
Clinical Case Reports · 2025 · 0 citations · open access
Kindler Syndrome: A Case Report From a Developing Country
AbstractKindler syndrome can be diagnosed clinically even in the absence of genetic testing. Early recognition of the disease, combined with regular surveillance for malignancy and a multidisciplinary approach that includes attention to psychosexual health, is essential for improving patient outcomes, enhancing quality of life, and promoting social integration.
Harper's Textbook of Pediatric Dermatology · 2011 · 0 citations
Kindler Syndrome
AbstractKindler syndrome is a rare autosomal recessive genodermatosis characterized by acral blisters in the neonatal period, followed by trauma-induced blister formation in early childhood, photosensitivity, generalized progressive poikiloderma, diffuse cutaneous atrophy and mucosal inflammation. The gene responsible for Kindler's syndrome is located on chromosome 20p.12.3. The skin fragility in Kindler's syndrome is a result of the loss of expression of an actin-cytoskeleton-associated protein named fermitin family homologue 1 (previously termed KIND-1).
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.
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