Transcript Is Lesion Permeability the Culprit in Cerebral Cavernous


Cavernous Malformation
 Thin walled, single layer of
endothelium, cluster of bubble-like
structures filled with stagnant blood
 Congenital or de novo
 Single or multiple

Sporadic CCM 80%
Familial CCM 20%

NM has highest density of inherited CM
worldwide
 Autosomal dominant disorder
 Common Hispanic founder mutation
 Hundreds of families
 Large families
 Multiple lesions
 All ages
 Geographic and cultural isolation
 Limited availability of neurological
and neurosurgical care in NM

Aim 1
Establish Registry @ University of New Mexico
500 CCM1-CHM patients
In collaboration with Angioma Alliance
Aim 2
Modifier genes: clinical variability
Lesion burden: primary outcome
Potential surrogate for adverse outcomes
Aim 3
longitudinal component
natural history data with detailed imaging
Aim 1: Database and
clinical factors
Yr1
Yr2
Yr3
Yr4
Yr5
X
X
X
X
X
X
X
X
X
Aim 2: GWAS and fine
mapping
Aim 3: Change in lesion
burden
X
X

The cerebral cavernous
malformation signaling
pathway promotes vascular
integrity via Rho GTPases.

Nat Med. 2009
Feb;15(2):177-84. Epub 2009
Jan 18

CCM2 mouse model, no
CCM’s but increased
permeability of skin

Decreased permeability of
skin with simvastatin
Anatomy and transfer rate in CCM: left to right, FLAIR image showing 3 CCMs; Ki (transfer rate) map; and VP (intravascular volume) map.
Saeid Taheri, PhD
Blaine L. Hart, M.D.
1) Use dynamic contrast-enhanced MRI (DCEMRI) to
detect abnormalities in brain permeability in CCM
patients and correlate with anatomic lesion information.
2) Compare change in permeability from baseline to three
months in a group of CCM patients placed on statin
medication with change in permeability for a control
group of CCM patients not on statin medication, which
could lay the basis for drug treatment trials for the
larger CCM community.
3) Develop plans for a large blinded prospective clinical
statin trial comparing outcome (number of
hemorrhages, worsening of epilepsy) using
permeability as a biomarker.