Primary Ciliary Dyskinesia (PCD) is a very rare hereditary systemic disease, which leads, amongst other things, to secretion retention and, as a result, to chronic inflammation and often also chronic respiratory tract infection. Until now, further investigation into this disease has been hampered by the limited amount of cell material available for research. Thanks to interdisciplinary cooperation, DZL scientists have now succeeded in producing induced pluripotent stem cells, with which unlimited amounts of test material can be manufactured.
Primary Ciliary Dyskinesia (PCD) is a rare, inherent and incurable airway disease. Patients with PCD suffer from chronic infections, inflammation and, as a result, sometimes even irreparable tissue damage. On the occasion of the International Rare Disease Day, we reported on the long path to diagnosis and the everyday limitations experienced by sufferers. The cause of the disease is a malfunction of the cilia of the respiratory epithelium, a special protective and functional layer of cells which line the airways. The molecular mechanisms of the disease development are as yet, however, still not completely clarified. Up to now, PCD-inducing mutations are known in about 50 genes, spanning from a malformation due to damage of the dynein arms of the cilia, through an abnormal beat pattern to complete lack of cilia (ciliary agenesis). Thus, transport of the respiratory secretions and also the moistening and cleaning of the airways will be impaired.
Currently, there is no approved and specific therapy for PCD. Often, treatment consists merely of treatment of the symptoms, reducing secretion sediment through inhalation and respiratory physiotherapy and controlling the frequent infections with antibiotics. Up to now, detailed studies have been hampered by a distinct lack of cellular material of reliable quality being available for researchers.
At BREATH, the Hannover site of the German Center for Lung Research (DZL), an interdisciplinary team led by the basic scientists Dr. Ruth Olmer and Prof. Ulrich Martin (Department of Cardiothoracic, Transplant and Vascular Surgery and the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); MHH) and the clinicians PD Dr. Felix Ringshausen (Senior Physician, Department of Respiratory Medicine; MHH) are working towards removing this bottleneck using a translational approach. The researchers have been successful in isolating blood cells from three PCD patients with different mutations in relevant genes (CCNO (missing cilia), DNAH5 (abnormal ultrastructure of the cilia) and NME5 (dysfunctional cilia)) and producing induced pluripotent stem cells from them. These cells can be multiplied infinitely in the laboratory and differentiated into ciliated airway cells. As a result of this, sufficient supplies of test material will be available to the researchers in future to develop an in vitro model of PCD.
Based on this new model, the causes of the disease will now be able to be investigated more closely and innovative targeted therapy options developed. This exciting and challenging task will be addressed by the team in the future.