As mentioned in last week’s blog, the International Rare Lung Diseases Research Conference (RLDC) was held in Cincinnati, USA, 22nd-25th September. Clinicians, scientists, patient organizations, patients and families were brought together to discuss research and clinical trials in rare lung disease and to promote dialogue between the research community and patients.
It is increasingly clear that some rare diseases share characteristics both in symptoms and underlying pathogenesis. Birt-Hogg-Dubé (BHD) syndrome is an example of this, sharing pulmonary, kidney and skin symptoms with a variety of other rare conditions. It is therefore important to stay informed about other rare conditions to avoid misdiagnosis and to understand that promoting research and trials in one rare disease may help the research development and the treatments of others.
Dr David Fajgenbaum from the University of Pennsylvania was responsible for the kick-off presentation. He shared his story of battling multicentric Castleman disease (MCD) as a physician-scientist-advocate-patient. In 2012 Dr Fajgenbaum funded the Castleman Disease Collaborative Network (CDCN) to connect the community of patients and researchers and to accelerate research in CD. Since then a lot has advanced in CD research with new models and treatment approaches (Fajgenbaum et al., 2016). Dr Fajgenbaum emphasized the importance of questioning the status quo and of collaboration among all stakeholders.
The FDA presented their work collaboration with the LAM foundation in the approval of Sirolimus treatment and their programs to help develop drugs in the rare disease field. There were several presentations about the current state of the art diagnostics and treatments for rare lung diseases:
- Dr Denise Adams from Harvard Medical School talked about Thoracic lymphangiomatosis. mTOR inhibitors were tested on patients with a good partial response (Ricci et al., 2015), however, there is no genetic understanding of how these diseases work. Dr Adams also mentioned the existence of patient registries and the use of Ang-2 as a biomarker.
- Dr Joseph Parambil from the Cleveland Clinic talked about Hereditary Hemorrhagic Telangiectasia, a genetic disorder with autosomal dominance caused by mutations in ENG, ACURL1 or SMAD4 and related to TGF-b The disease has several pulmonary manifestations.
- Dr Kristin Highland talked about Sjogren Syndrome, a female predominant chronic systemic autoimmune disease commonly associated with follicular bronchiolitis, interstitial lung disease, pulmonary amyloidosis and pulmonary lymphoma.
- Dr Timothy Blackwell talked about Familial Interstitial Pneumonia, a highly genetic autosomal dominant disease with incomplete penetrance associated with RTEL1
- Dr Enid Neptune from Johns Hopkins University presented the Marfan Syndrome (MFS) as a template for dissecting multisystem single gene disorders. Mutations in fibrillin-1, which bears homology to TGF-b binding proteins, are found in MFS patients. MFS patients present spontaneous pneumothorax and there is enhanced TGF-b activation in patients with pulmonary symptoms.
- Dr JP Clancy gave a talk about Cystic Fibrosis and possible therapies for the disease including the use of cystic fibrosis transmembrane regulator (CFTR) modulators like Ivacaftor, gene transfer and gene/RNA editing.
- Dr Laurie Carr talked about Difuse Idiophatic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH), a disorder of the bronchopulmonary neuroendocrine cells with 195 cases reported so far usually in middle-aged women. The disease is often misdiagnosed as asthma even though it has distinct features such as multiple scattered pulmonary nodes. The current treatment is an Octreotide based therapy – a synthetic analogue of somatostatin, a hormonal peptide.
- Dr Bruce Trapnell discussed Pulmonary alveolar proteinosis (PAP), a male-prevalent disease associated with disruption of GM-CSF signalling, macrophage function and surfactant structure.
- Dr Francis McCormack, the conference scientific chair, talked about Pulmonary Alveolar Microlithiasis (PAM), a disease associated with filling of alveolar space with calcium phosphate microliths with 1022 cases reported. PAM is associated with mutations in SLC34A2.
- The session ended with a presentation by Dr Nishant Gupta about Light-Chain Deposition Disease (LCDD), a very rare disease characterized by deposition of non-fibrillary amorphous material in various tissues that has renal failure as a common symptom. Diffuse cystic lung disease in LCDD can mimic other common diffuse cystic lung diseases such as LAM. Matrix degradation by MMPs may lead to cyst formation in LCDD.
- In a session named “Cystic Lung Disease”, Dr McCormack gave a presentation about lymphangioleiomyomatosis (LAM) and all the LAM clinical trials including the MILES and TRAIL trials and the MIDAS study.
- Dr Kotloff presented BHD Syndrome – a summary of this talk can be find on last week’s blog post.
- Dr Abdellatif Tazi presented Langerhans Cell Histiocytosis (LCH), a rare disease characterized by tissue infiltration with Langerhans-like dendritic cells, usually organized into granulomas. Lung pathology includes focal granulomas. The MAKP pathway is known to be involved in LCH.
The RLDC 2016 Cincinnati was the largest and most comprehensive international rare lung disease meeting, bringing together physician-scientists and patient advocates to discuss rare lung disease research and treatments. Patients and families also gave presentations and were encouraged to learn, inspire, and collaborate.
- McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee (2011). Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis New England Journal of Medicine, 365 (3), 271-272 DOI: 10.1056/NEJMc1106358