Post on 19-Jan-2021
RASopathies
Symposium
Fourth International
July 17-19, 2015Doubletree by Hilton at SeaTacCo-Chairs: David A. Stevenson, MD and Brigitte Widemann, MD
Investigators: Lisa Schoyer, PI and Lisa Schill, Co-PI
RASopathies
Symposium
Fourth International
THANK YOU TO OUR SPONORSplatinum
This symposium was funded in part
by the following National Institutes of Health
through grant no. 1R13TR001272-01:
The National Center for Advancing Translational Sciences (NCATS)
The National Cancer Institute (NCI)
The National Institute of Neurological Disorders and Stroke (NINDS)
The National Institute of Child Health and Human Development (NICHD)
Gold
Silver
Bronze
Exhibitor
S)
Treatment of stature using CNP
Short stature and craniofacial abnormalities are common findings in patients with RASopathies.
However, the etiology of these conditions remains unknown, and available treatments to promote
growth are not devoid of risk. Preclinical research focused on the skeletal maladies associated with
FGFR3 activating mutations and neurofibromatosis type 1 (NF1) highlighted the importance of
properly regulated RAS/ERK signaling during the process of endochondral formation, which give the
skeleton its size and shape. These studies revealed that chronic activation of RAS/MEK/ERK
signaling in growth plate chondrocytes, triggered by activating mutations in FGFR3 or NF1 loss of
function, impairs their differentiation and function, leading to short stature and impaired bone healing.
In both conditions, RAF-1 inhibition by C-type Natriuretic Peptide (CNP) improved bone growth in
preclinical animal models; a pharmacokinetically stable, recombinant version of CNP is currently in
clinical trials for the treatment of dwarfism caused by FGFR3 mutations. CNP thus represents a
potential targeted therapeutic drug to improve the stature of patients affected with disruption of the
RAS/MEK/ERK pathway.
CHANGE HOW YOU SEE, SEE HOW YOU CHANGE
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