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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