A newly discovered disease may lead to better treatment of cystic
fibrosis

Date:
June 5, 2020
Source:
University of Mu"nster
Summary:
Cystic fibrosis is the most frequent severe inherited disorder
worldwide.

Researchers have now discovered a novel disease that might lead
to a better understanding of cystic fibrosis and new treatment
options in the future.



FULL STORY ========================================================================== Cystic fibrosis is the most frequent severe inherited disorder
worldwide. Every year, hundreds of families are confronted with this
diagnosis -- and to date, there is no cure for this disease that mainly
affects the respiratory system.

Besides supportive treatments, a lung transplant is often the only option
to save a patient's live. Researchers of the Universities of Mu"nster
and Regensburg have now discovered a novel disease that might lead to
a better understanding of cystic fibrosis and new treatment options in
the future. The results have been published in the scientific journal
Journal of Medical Genetics.


==========================================================================
The cause of cystic fibrosis are mutations in the cystic fibrosis
transmembrane conductor regulator gene (CFTR). This gene contains
the blueprint for a chloride channel on the surface of cells in the
body. Normally, this channel mediates the accumulation of salt and fluids
on the surface of the airways thereby leading to a continuous cleaning
of the airways. Defects in the CFTR channel prevent the transport of
chloride ions and thus the humidification of the respiratory tract. As
a result, the airways of affected individuals literally get plugged by
a thickened, viscous mucus that leads to airway obstruction -- patients
are at the risk of suffocating.

At the University of Mu"nster, the lab of Prof. Thorsten Marquardt
has now discovered a new disease that is caused by defects in another
chloride channel, TMEM16A. This channel is also present on the surface
of airway cells. In cooperation with the lab of Prof. Karl Kunzelmann of
the University of Regensburg, the researchers evaluated the cellular
effects of the disorder that is caused by a total loss of TMEM16A
function. Surprisingly, they discovered that not only TMEM16A but also
CFTR is not functional in these patients.

Excitingly, this has the potential to improve the treatment of patients suffering from cystic fibrosis.

"We were astonished that children with TMEM16A deficiency don't have
any respiratory symptoms at all. A loss of CFTR function due to lack
of TMEM16A does not lead to clinincal symptoms of cystic fibrosis in
these kids," states Dr. Julien Park, first author and researcher at the Marquardt lab at the Department of General Pediatrics at the University Hospital Mu"nster.

Similarly, the group of Prof. Karl Kunzelmann found in a mouse model
that a double knock out of CFTR and TMEM16A does not develop lung disease.

Taken together, these results raise an intriguing question: Could the pharmacological inhibition of TMEM16A improve the respiratory symptoms
of patients with cystic fibrosis? A significant reduction of mucus
production and secretion as a consequence of TMEM16A inhibition has
previously been shown under laboratory conditions. The researchers want
to study this approach further in the future: "As a next step, we are
planning clinical trials to evaluate a treatment of cystic fibrosis with TMEM16A inhibitors," states Karl Kunzelmann.


========================================================================== Story Source: Materials provided by University_of_Mu"nster. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Julien H Park, Jiraporn Ousingsawat, Ine^s Cabrita, Ruth E Bettels,
Jo"rg
Grosse-Onnebrink, Christian Schmalstieg, Saskia Biskup, Janine
Reunert, Stephan Rust, Rainer Schreiber, Karl Kunzelmann, Thorsten
Marquardt.

TMEM16A deficiency: a potentially fatal neonatal disease resulting
from impaired chloride currents. Journal of Medical Genetics,
2020; jmedgenet- 2020-106978 DOI: 10.1136/jmedgenet-2020-106978 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200605140505.htm

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