DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial spontaneous pneumothorax — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial spontaneous pneumothorax maps to a 3-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 familial spontaneous pneumothorax 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
serpin family A member 1 (SERPINA1) — SERPINA1 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 5rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1IZ2 · 2.2 Å · ligand (5R)-5-[(2R)-2-hydroxynonyl]-beta-D-xylulofuranose (Z6W). Experimental structure, not a prediction.
What the evidence adds up to
In 12 families with at least two first-degree relatives who had a spontaneous pneumothorax and no signs of known genetic disorders, two families were found to carry nonsense mutations in the FLCN gene. These mutations are the same ones that cause Birt-Hogg-Dubé syndrome, a rare autosomal dominant condition that includes skin lesions, renal tumours, and pulmonary blebs. None of the affected family members had skin manifestations or renal cancer. Lung tissue from three non-smokers showed blebs and underlying emphysema. A separate report describes a 34-year-old Filipino male with recurrent pneumothorax, a sibling who also had a pneumothorax, and CT findings of multiple thin-walled cysts predominantly in the lower lobes and paramediastinal regions; abdominal ultrasound found no renal masses. The authors note that only 5% of male Birt-Hogg-Dubé patients present with isolated pneumothorax, and that 9% of patients presenting with spontaneous pneumothorax may have Birt-Hogg-Dubé syndrome.
A large family with frequent consanguineous marriages contained eight individuals affected by primary spontaneous pneumothorax. The authors propose autosomal recessive inheritance based on the pedigree, but no molecular genetic analysis was performed. In another case, a 30-year-old man with recurrent pneumothorax had a father and two elder sisters who also had relapsed primary spontaneous pneumothorax despite pleurodesis and bullectomy; the pattern suggested autosomal dominant inheritance. A review notes that pneumothorax can be the herald manifestation of several genetic syndromes with serious extrapulmonary complications, including malignant renal tumours in Birt-Hogg-Dubé syndrome, and provides an algorithm for deciding when to pursue genetic testing.
Three patients aged 24 to 37 with daily marijuana use for 10 to 14 years and heavy tobacco use (11 to 50 pack-years) each suffered a spontaneous pneumothorax. The authors suggest marijuana may accelerate tobacco-induced lung disease and that the Valsalva manoeuvre during smoking may contribute. A separate review states that clinical studies on spontaneous pneumothorax treatment are small and few, and practice remains variable. The 2017 review on familial pneumothorax emphasises that the pneumothorax often precedes more dangerous complications by many years, offering an opportunity for early intervention, but does not provide new trial data.
What is still missing: prospective studies that systematically screen pneumothorax patients for FLCN and other mutations, trials comparing surveillance strategies for those with identified genetic risk, and cost-effectiveness data for genetic testing in resource-limited settings where most cases occur. No drug treatment for familial pneumothorax has been tested in any of these reports.
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 Respiratory and Critical Care Medicine · 2005 · 116 citations
Nonsense Mutations in Folliculin Presenting as Isolated Familial Spontaneous Pneumothorax in Adults
AbstractRATIONALE: Approximately 10% of patients who have a spontaneous pneumothorax have a positive family history. OBJECTIVES: We sought to identify DNA sequence variations that confer susceptibility to pneumothoraces. METHODS: We collected 12 families that had at least 2 first-degree relatives with a spontaneous pneumothorax. All affected family members had no obvious stigmata of known genetic disorders associated with pneumothoraces. We used haplotype analysis, DNA sequencing, and restriction fragment analysis of mutations to evaluate the individuals in these families. MAIN RESULTS: In 2 of the 12 families the disorder cosegregated with markers flanking a candidate locus, FLCN. Sequencing the linked alleles revealed 2 mutations predicted to introduce premature stop codons in 2 of the 12 families. Most mutations in FLCN cause a rare disease, Birt-Hogg-Dubé syndrome, characterized by autosomal dominant inheritance of multiple benign skin lesions, renal tumors, pulmonary blebs, and pneumothoraces. None of the family members with the nonsense mutations had the skin manifestations of Birt-Hogg-Dubé syndrome or renal cancer. Pathologic examination of lung tissue from three affected nonsmokers revealed blebs and underlying emphysema. CONCLUSIONS: Isolated familial spontaneous pneumothorax can be caused by mutations of the FLCN gene. Because development of a pneumothorax and/or pulmonary blebs may be the earliest or the only clinical manifestation of FLCN mutations, pulmonologists should be alert to the contribution of this gene toward this familial form of emphysema.
Journal of Substance Abuse · 1993 · 50 citations · open access
Pneumothorax in polysubstance-abusing marijuana and tobacco smokers: Three cases
AbstractThree patients are reported who suffered spontaneous pneumothorax, each of whom also had a history of daily marijuana and tobacco use. The patients ranged in age from 24 to 37 years, had smoked marijuana on a daily basis for 10 to 14 years, and had 11 to 50 pack-year tobacco-smoking histories. Marijuana may predispose to pneumothorax both by accelerating tobacco-induced lung disease, and by the frequent performance of the Valsalva maneuver during marijuana smoking. Although there is an association between pneumothorax and heavy tobacco use, an association with chronic daily marijuana use has not previously been reported.
AbstractOne in 10 patients suffering from primary spontaneous pneumothoraces has a family history of the disorder. Such familial pneumothoraces can occur in isolation, but can also be the presentation of serious genetic disorders with life-threatening vascular or cancerous complications. As the pneumothorax frequently precedes the more dangerous complications by many years, it provides an opportunity to intervene in a focused manner, permitting the practice of precision medicine. In this review, we will discuss the clinical manifestations and underlying biology of the genetic causes of familial pneumothorax.
Journal of Thoracic Disease · 2017 · 1 citations · open access
Needle aspiration should be considered as primary intervention option for stable patients with spontaneous pneumothorax
AbstractPatients with spontaneous pneumothorax are treated by clinicians of different medical specialties worldwide with slightly different approaches. Handling of patients ideally should be based on best evidence in guidelines, but practice is still to a large extent variable and depending on local clinical experience. Clinical studies are small and few on the subject.
American Journal of Respiratory and Critical Care Medicine · 2025 · 0 citations
Recurrent Isolated Pneumothorax Unveiling a Familial Multicystic Lung Disease in a 34-Year-Old Filipino Male
AbstractAbstract INTRODUCTION: Spontaneous pneumothorax (SP) often occurs due to rupture of subpleural blebs or cysts, with an incidence of 1.2-7.4 cases/100,000. 11.5% exhibit familial predisposition. In resource-limited settings, genetic testing is often unavailable, prompting reliance on advanced imaging techniques to narrow differentials or establish a diagnosis. Here, we present a unique case of recurrent SP in a young male with multicystic lung disease with notable family history of pneumothorax. CASE: A 34-year-old Filipino male, eight pack-year smoker and illicit drug user, presented with a one-week history of worsening dyspnea and pleuritic chest pain. He had previously been admitted at age 24 for a pneumothorax, which resolved with conservative management. Family history was significant for a sibling who underwent surgical intervention for a pneumothorax one year prior. He denied bouts of respiratory infections, congenital connective tissue or lung disorders, skin lesions, or unusual skin elasticity. On examination, he was hypotensive (90/60 mmHg), tachycardic (101 bpm), and tachypneic (23 breaths per minute), with an oxygen saturation of 90% on room air. Decreased breath sounds and reduced vocal fremitus were noted on the right side, extending from the apex to the lower lung fields. A chest radiograph revealed a right-sided tension pneumothorax with mediastinal shift and large lucent lesions without lung markings in the left retrocardiac area (measuring 4.5 x 4.9 cm and 3.7 x 3.2 cm). A chest tube was placed, resolving the pneumothorax, as confirmed on repeat radiographs. Subsequent chest CT showed multiple variably-sized, thin-walled air cysts on both lungs, the largest in the left basal lower lobe, measuring 3.0 x 4.4 x 7.9 cm, near the mediastinum. Abdominal ultrasound excluded renal masses. Following pneumothorax resolution, he underwent pleurodesis and was discharged in stable condition. DISCUSSION: Diffuse cystic lung disease (DCLD) encompasses a broad spectrum of slowly progressing rare conditions but significant differential diagnosis and complications. A family history, distinctive clinical features, and specific radiographic findings can help guide the diagnosis. Familial DCLD with predominant lower-lobe, paramediastinal cysts and recurrent SP—such as in our patient—often points to Birt-Hogg-Dubé syndrome (BHD), a rare autosomal-dominant disorder associated with cystic lung disease, skin lesions, and renal tumors. BHD is thought to be rare, though its prevalence remains unknown, and studies suggest a 9% likelihood of BHD in patients presenting with SP. However, only 5% of male BHD patients present with isolated pneumothoraces, as in this case, emphasizing the variability in presentations of this intriguing syndrome.
Turkiye Klinikleri Archives of Lung · 2016 · 0 citations · open access
Autosomal Recessively Inherited Familial Primary Spontaneous Pneumothorax: A Large Family with Frequent Consanguineous Marriages
AbstractObjective: The objective of this study is to determine the clinical and hereditary characteristics of Familial Primary Spontaneous Pneumothorax (FPSP) observed in a number of individuals within a large family. Material and Methods: In the medical history of the patient, WHO applied to the Emergency Department due to a severe difficulty in breathing and was diagnosed with a bilateral Primary Spontaneous Pneumothorax (PSP) and received a bilateral tube thoracostomy performed by the pediatric surgery clinic, it was determined that there were 8 individuals in his family circle who had been affected by PSP disease. All the demographic, clinical, laboratory, radiological, and hereditary data of these individuals were collected. Results: In the physical examination of the patients, there were incisional scars of tube thoracostomy and/or thoracoscopy and/or thoracotomy over the rib cages of 6 cases. While the other system examinations and laboratory findings were normal of all patients, seven of the cases have radiological changes at low- and mid- levels - in the lungs in the thoracic computerized tomography. Based on the drawn family tree, we suggest that the FPSP in this family occurred through autosomal recessive heredity. Conclusion: We believe that the PSP seen in this family is familial and transferred through autosomal recessive inheritance and the common consanguineous marriages within the family plays a role in the intensity of the disease. Further research on molecular level is required in order to better understand the precise genetic reasons that are lying under the developed FPSP disease of these eight patients.
Apollo (University of Cambridge) · 2019 · 0 citations · open access
The Genetics of Pneumothorax.
AbstractA genetic influence on spontaneous pneumothoraces-those occurring without a traumatic or iatrogenic cause-is supported by several lines of evidence: 1) pneumothorax can cluster in families (i.e., familial spontaneous pneumothorax), 2) mutations in the FLCN gene have been found in both familial and sporadic cases, and 3) pneumothorax is a known complication of several genetic syndromes. Herein, we review known genetic contributions to both sporadic and familial pneumothorax. We summarize the pneumothorax-associated genetic syndromes, including Birt-Hogg-Dubé syndrome, Marfan syndrome, vascular (type IV) Ehlers-Danlos syndrome, alpha-1 antitrypsin deficiency, tuberous sclerosis complex/lymphangioleiomyomatosis, Loeys-Dietz syndrome, cystic fibrosis, homocystinuria, and cutis laxa, among others. At times, pneumothorax is their herald manifestation. These syndromes have serious potential extrapulmonary complications (e.g., malignant renal tumors in Birt-Hogg-Dubé syndrome), and surveillance and/or treatment is available for most disorders; thus, establishing a diagnosis is critical. To facilitate this, we provide an algorithm to guide the clinician in discerning which cases of spontaneous pneumothorax may have a genetic or familial contribution, which cases warrant genetic testing, and which cases should prompt an evaluation by a geneticist.
AbstractWe experienced a case of familial spontaneous pneumothorax (SP) without apparent underlying connective tissue disease. A 30-year-old man was referred to our hospital complaining of slight dyspnea and right chest pain due to recurrent SP. The patient had two episodes of primary SP of the right lung, and received chest tube drainage, pleurodesis and surgical bullectomy. Otherwise, his father and two elder sisters also had relapsed primary SP in spite of recurrent prevention therapies. This transmission pattern of the disease phenotype suggested an autosomal dominant inheritance. There have been improvements in pathogenesis, diagnostic procedures and recurrence prevention therapies, but this familial case still suffers from recurrent SP. This familial case may strongly require a new therapeutic strategy for familial SP.
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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