Page 12 - 2021 Spring CMTA Report - Special Research Edition
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STAR’s Portfolio for
Demyelinating CMTs - 1A, 1B, 1X
(and some 4s)
NORMAL NERVE
NERVE AFFECTED
Nerves are bundles BY CMT
of many nerve fibers, most of
them wrapped in myelin.
Myelin is an insulating and
protective coating formed by
Schwann cells that make nerve
MYELIN SHEATH impulses much faster
(from 1 to >50 meters/second).
Myelin problems cause
demyelinating CMT (CMT1).
DAMAGED MYELIN Problems with nerve fibers
(i.e., axons, long extensions of
nerve cells transmitting
signals) cause axonal
CMT (CMT2).
EXPOSED FIBER
NERVE FIBER (AXON)
(AXON)
NERVE FIBER
(AXON)
Demyelinating forms of CMT affect have shown that gene therapy is mind that we have a clear pathway for
the protective coating, or myelin, feasible in rodent models of CMT1X treatment of CMT2 type neuropathies
that insulates the “electrical wire” and CMT4C, and the CMTA is actively that affect motor neurons. The
that is the nerve. Research specific to supporting the efforts of several gene recently approved AAV treatment
demyelinating forms of CMT—Types therapy companies to develop new for spinal muscular atrophy lays the
1A, 1B, 1X and some Type 4s—includes CMT gene therapies. Pioneering technological groundwork for similar
some two dozen projects: CMTA-sponsored preclinical gene treatments for CMT2A and others.
GENE THERAPY AND therapy studies have shown great However, for CMT1A, it is not yet clear
if AAV9 will be the optimal vehicle
promise in models of demyelinating
GENE EDITING PROJECTS CMT. This approach is now being for Schwann cell delivery. Because of
In collaboration with Ionis extended to use RNA interference to this, we are supporting a
Pharmaceuticals, we are developing decrease the PMP22 levels found in collaborative relationship to build on
antisense oligonucleotides (ASOs), CMT1A and to optimize delivery to Dr. Kleopa’s success in fixing Schwann
which have shown dramatic results the affected Schwann cells in cell deficits in preclinical trials for
in two rodent models of CMT1A. demyelinating CMT. CMT1X and CMT4C. The partnership
CMTA-funded studies by As the CMTA engages various of Dr. Kleopa with an eminent gene
Dr. Kleopas Kleopa of the Cyprus partners to initiate gene therapy therapy expert, Dr. Steven Gray, and
Institute of Neurology and Genetics projects, it is important to keep in an expert in Schwann cell specific
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