DeCure for T-cell immunodeficiency, congenital alopecia, and nail dystrophy
DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for T-cell immunodeficiency, congenital alopecia, and nail dystrophy — 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 moduleT-cell immunodeficiency, congenital alopecia, and nail dystrophy 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 t-cell immunodeficiency, congenital alopecia, and nail dystrophy 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
forkhead box N1 (FOXN1) — FOXN1 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 6EL8 · 1.61 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2016 case report describes a male patient with alopecia areata universalis whose nail dystrophy, including striated lunulae, pitting, and trachyonychia, prevented him from playing the guitar. After 10 months of tofacitinib 5 mg twice daily, his nail changes and function showed remarkable improvement. A 2024 case report describes a patient with persistent alopecia areata-associated nail changes, including periungual inflammation, ridges, and pitting, that had not responded to tacrolimus, clobetasol, or oral fluconazole. After 4 months of baricitinib, mild improvement was seen with some clubbing and pitting still present; after 11 months, the nail was normal in appearance and texture. A 2021 case report describes an 8-year-old boy with trachyonychia, alopecia areata, and lichen planus who was successfully treated with biweekly pulse systemic corticosteroid therapy for 6 months, with significant improvement in hair regrowth, nail texture and thickness, and resolution of skin lesions.
A 2017 report describes two siblings with congenital alopecia universalis and twenty-nail dystrophy. Skin biopsy was suggestive of alopecia areata, and the authors note that alopecia areata is an autoimmune disease with a genetic predisposition. A 2020 report describes two siblings with alymphoid cystic thymic dysgenesis caused by a FOXN1 gene mutation. The first child, a 7-month-old female, had alopecia totalis, nail dystrophy, failure to thrive, BCG adenitis, and combined T and B cell immunodeficiency; bronchoalveolar lavage was positive for Mycobacterium tuberculosis and Pneumocystis carinii pneumonia. Genetic analysis revealed a recessive missense mutation in exon 6 of FOXN1. The second child had similar phenotypic features and very low lymphocyte subset counts.
The 2024 baricitinib report explicitly states there are no established guidelines to treat alopecia areata-associated nail changes and that further research is needed to determine which patients may benefit and when treatment should be initiated. The 2016 tofacitinib report is a single case. The 2020 FOXN1 report notes the mutation was initially classified as a variant of unknown significance due to lack of sufficient literature. What is still missing are controlled trials with adequate sample sizes, standardised outcome measures for nail changes, and clear stratification of patients by genetic aetiology — particularly distinguishing autoimmune alopecia areata from syndromic forms like FOXN1 deficiency, which involve T-cell immunodeficiency and may require fundamentally different management.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Case Reports in Dermatology · 2016 · 35 citations · open access
Remarkable Improvement of Nail Changes in Alopecia Areata Universalis with 10 Months of Treatment with Tofacitinib: A Case Report
AbstractAlopecia areata (AA) is a chronic, autoimmune disease. The main symptom is massive hair loss, localized or diffuse, in the scalp and the whole body. However, nails may also be involved, and brittleness, fragility and pitting can be signs of nail dystrophy in AA patients. Here, we report the case of a male patient with AA refractory to various treatments, including oral, topical and intralesional corticosteroids, immunosuppressants, cyclosporin and PUVA (oxoralen plus ultraviolet light), all interrupted due to side effects. The patient's nails had erythematous blotches (striated lunulae) with regular and superficial pitting as well as fragility (trachyonychia), and he could no longer play the guitar because of these symptoms. With patient consent, we introduced tofacitinib (5 mg twice daily), which resulted in remarkable improvements not only regarding hair regrowth but also nail changes, with function recovery within 10 months.
International Journal of Trichology · 2017 · 5 citations · open access
Rare presentation of alopecia universalis congenita and twenty-nail dystrophy in siblings
AbstractCongenital alopecia universalis is one of the rarest anomaly which involves skin and appendages. The inheritance pattern can be autosomal recessive, X-linked recessive, or autosomal dominant. However, the most common is autosomal recessive form and it is the most severe phenotype. Twenty-nail dystrophy refers to the condition in which all the twenty nails are affected in the form of excessive ridging and nail plate roughness leading to unsightly lustureless nails. We report a rare case of two siblings with alopecia universalis congenita with twenty-nail dystrophy. To the best of our knowledge, this case is the first case to be reported with such association in both siblings. This case reports highlights the fact that alopecia areata is an autoimmune disease with a genetic predisposition as in our case both siblings had alopecia universalis and nail dystrophy. There was no evidence of any other ectodermal dyplasia and had normal teeth and seat glands. The skin biopsy ruled out congenital atrichia and was suggestive of alopecia areata.
Case Reports in Dermatological Medicine · 2024 · 5 citations · open access
Therapeutic Response of Alopecia Areata‐Associated Nail Changes to Baricitinib
AbstractNail changes are seen in some individuals with alopecia areata, with the most common variants including pitting and trachyonychia. The nail findings are presumed to be due to the same lymphocytic infiltration seen in hair bulbs in individuals with AA. Baricitinib is an immunomodulatory drug that acts as a selective and reversible inhibitor of JAK proteins and is indicated for adult patients with moderate to severe rheumatoid arthritis who have not responded to other disease-modifying antirheumatic drugs. The FDA has also approved baricitinib to treat patients hospitalized with COVID-19 and severe alopecia areata. In this report, we present a case of a patient with persistent AA-associated nail changes who has been successfully treated with baricitinib. The patient has been suffering from alopecia for several years. She presented with periungual inflammation in conjunction with persistent fingernail ridges and pitting of her right fourth digit. The nail dystrophy persisted despite treatment with tacrolimus ointment, clobetasol ointment, or oral fluconazole. Patient was started on a trial of baricitinib for alopecia areata, which was the suspected cause of the nail changes. After 4 months of treatment with baricitinib, the patient's nail showed mild improvement of nail dystrophy with some clubbing and pitting still present. Within 11 months of treatment, her nail was normalized in appearance and texture. There are no established guidelines to treat AA-associated nail changes. Our patient's AA-associated nail changes were normalized after 11 months of treatment with baricitinib. Further research is needed to determine which alopecia areata patients may benefit from treatment with baricitinib and when treatment should be initiated. Baricitinib may be an effective treatment option for AA-associated nail changes in some patients.
International Journal of Research in Dermatology · 2021 · 0 citations · open access
Trachyonychia in a child with concomitant alopecia areata and lichen planus
Abstract<p>Trachyonychia of nails has been found to be associated with dermatoses such as lichen planus, psoriasis, alopecia areata etc. When involving all the finger and toe nails bilaterally, it is referred to as ‘twenty nail dystrophies. We, hereby, report a case of trachyonychia in an 8-year-old boy, with concomitant lichen planus and alopecia areata. He was successfully treated with biweekly pulse systemic corticosteroid therapy for duration of 6 months. Significant response was noted at the end of 6 months in terms of hair re-growth; improvement of nail texture, thickness and subungual hyperkeratosis; and resolution of skin lesions.</p>
International Journal of Contemporary Pediatrics · 2020 · 0 citations · open access
Alymphoid cystic thymic dysgenesis - FOXN1 gene mutation: a rare case report of two siblings
AbstractAlymphoid cystic thymic dysgenesis is a severe combined immunodeficiency (SCID) syndrome caused b y a mutation in fork head box N1 gene (FOXN1) on chromosome 17. It is a transcriptional factor regulating the development, differentiation and function of thymic epithelial cells; maintaining T-lineage progenitors in bone marrow; promoting terminal differentiation of epithelial cells of hair follicles. Mutation in FOXN1 is known to cause a rare disorder characterized by rudimentary thymus gland (primary lymphoid organ for T-cell differentiation), T-cell immunodeficiency, congenital alopecia totalis and nail dystrophy. Here we report two affected siblings from a non-consanguineous family with similar features of alopecia totalis, nail dystrophy and failure to thrive. The first child was a 7-month-old female baby, with history of two hospitalization in the past for lower respiratory tract infection, had left axillary lymphadenopathy (BCG adenitis), alopecia totalis, nail dystrophy and hepatosplenomegaly. Bronchoalveolar lavage secretion was positive for Mycobacterium tuberculosis and Pneumocystis carinii pneumonia by gene Xpert and polymerase chain reaction respectively. Immunodeficiency panel workup revealed combined T cell and B cell immunodeficiency, genetic analysis by whole exome sequencing revealed recessive missense mutation in exon 6 of FOXN1 gene on chromosome 17. Due to lack of sufficient literature it was reported as variant of unknown significance and to establish its clinical significance the carrier status of both the parents was established. Second child presented to us at 3 months of age, also had similar phenotypic features and on evaluation had very low lymphocyte subset count however mutational analysis could not be done in this child due to parent’s denial. Hence, we conclude this child also was affected.
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.
