Page 6 - 2020 Spring CMTA Report

CMTA BOARD AWARDS $856,000

FOR CMT1B, 2E STUDIES

CMT2E GENE THERAPY hypothesis that both recessive and (COA) that include neurological
dominant forms of disease result examinations, testing of patients’
COLLABORATION from lost function of NEFL. functional ability to perform tasks,

The study’s goal is to evaluate and evaluation of patient-reported
he CMTA Board of Directors
gene therapy strategies for restoring questionnaires. Natural history
voted to fund a $256,000
neurofilaments to diseased neurons data is lacking for CMT1B.
Tresearch project on CMT2E at
in Type 2 mice. If the approach is For clinical trials, natural his-
its March meeting. The study is
successful, the preclinical studies tory data also requires sensitive
aimed at enabling development of
will set the stage for obtaining biomarkers that can show that a
CMT2E gene therapy by showing
approval for clinical trials. therapy is reaching its target and
that it can be beneficial for this
effecting change within a single
axonal form of CMT affecting
motor neurons. CMT1B NATURAL HISTORY/ year. The newly approved project
The project involves a new BIOMARKERS STUDY aims to develop protein biomark-
collaboration among the Ohio ers, such as neurofilament L,
which can be identified in blood
State University labs of Anthony he Board also approved a
Brown, PhD, Arthur Burghes, new research project aimed at samples, and RNA biomarkers,
PhD, Kathrin Meyer, PhD, and Tcollecting natural history data which can be identified in skin
biopsies, that can be used to detect
W. David Arnold, MD. Several and developing biomarkers for
members of the team were CMT1B at its March meeting. changes in myelinating Schwann
Members of cells using a minimally invasive
involved in the development of CMT1B is caused by muta-
the CMT2E gene therapy for spinal muscular tions in the myelin protein zero technique. MRI imaging of
collaboration atrophy from mouse models to (MPZ) gene, the major protein in patients’ legs will also be used
developed patients. the myelin insulation that sheaths because the accumulation of fat in
The labs have complementary the nerve fiber, or axon. Over time muscles damaged by neuropathy
gene therapy can be measured very precisely as
expertise in neurofilament biology, CMT1B axons degenerate because
for spinal mouse genetics, gene therapy, viral of the abnormal MPZ in myelin, a measure of progression.
muscular vectors, neurodegenerative disease causing weakness, problems with The National Institutes of
atrophy. and electrophysiological assess- balance and impaired ability to Health recently funded a project
ments of neuromuscular function. feel touch. to obtain skin and serum samples
CMTA Scientific Advisory Board Multiple therapeutic strategies from 20 CMT1B patients for
(SAB) reviewers called the collabo- to treat Schwann cells—the cells biomarker analysis, but the diver-
ration a strength of the proposal that make the myelin—or to sity of CMT1B presentations
“that greatly enhances the likeli- preserve axons are underway for required additional samples.
hood of success.” The investigators CMT1B. These therapies are The new project will evaluate
have a history of productive designed to slow the disease and 60 patients with CMT1B over
collaboration and translation of include: Sephin1—a molecule two years and recruit patients not
preclinical studies to clinical trials. that has been shown to help some just from Dr. Michael Shy’s clinic
CMT2E is caused by MPZ mutant Schwann cells fold at the University of Iowa, but also
dominant mutations in the neuro- MPZ more efficiently—and from other sites in the Inherited
filament protein L (NEFL) gene, inhibition of proteins called Neuropathies Consortium,
but there are also some individuals Sarm1 and HDAC6, which including leading CMT clinics
with CMT who have recessive are both designed to minimize in London, Milan, Rochester,
mutations in the same gene. axonal degeneration. New York, and at the University
According to the SAB review Measuring disease pro - of Pennsylvania.
summary, the proposal addresses gression, or natural history, is The CMTA recently secured
unresolved questions about challenging in diseases like CMT commitments of $600,000 from
the underlying mechanism for that progress slowly, requiring two families toward the $601,280
CMT2E, proposing as a unifying clinical outcome assessments cost of the project. h

6 THE CMTA REPORT SPRING 2020