Page 13 - 2021 Spring CMTA Report - Special Research Edition

gene expression, Dr. John Svaren, will PREPARING FOR
address these challenges by trying
multiple AAV subtypes and optimizing CLINICAL TRIALS
the vector engineering so that we can In partnership with the Inherited
build in the necessary safety factors Neuropathy Consortium, we are
and optimal administration of AAV building on their recent successes
vector so that we can efficiently target in development of novel biomarkers
Schwann cells and move to clinical and outcome measures in CMT1A and
trials for CMT1A. These collaborative supporting major efforts to extend
efforts will provide the basis of future development and testing of critical
partnerships as we engage in parallel biomarkers for CMT1B and CMT1X
testing of several strategies to to support upcoming clinical trials.
determine which vector designs are Toward that end, the CMTA Board of
most effective. Directors awarded $601,407 in
January for a CMT1X biomarkers
We are currently collaborating with project that will evaluate 60
one company to use CRISPR (genome patients over two years, measuring
editing) to treat demyelinating CMT, progression using outcome measures
and additional collaborations with and biomarkers.
leading labs are underway. Clinical outcome assessments Lucas (left), a passionate
SMALL MOLECULE AND (COAs) are measures that have been footballer, was diagnosed with
BIOLOGICAL THERAPY developed to evaluate the clinical CMT1A at the age of 8, the

PROJECTS severity and progression of CMT over only one in his family to carry
time. Biomarkers are chemicals in the
In partnership with InFlectis body that reside in fluids like blood the gene.
BioScience, we are developing agents and tissues. Biomarkers are more
to restore myelin protein balance for sensitive than COAs, meaning that
CMT1A and CMT1B. Phase 1 clinical they measure changes over shorter The CMT Functional Outcome
trials have concluded, and InFlectis is periods of time, and therefore can Measure—This is a newer,
gearing up for Phase 2 trials. more quickly and precisely measure performance-based measure that
The progression of all types of CMT whether a treatment or drug had a assesses the functional ability of
occurs as the longest axons are positive impact on the neuropathy. adults with CMT. Performance
compromised in a process called axon COAs used in the CMT1X study will measures include strength in hands
degeneration. We are working with include: and feet, lower and upper limb
partners to develop molecules functioning (hand and finger dexterity),
that regulate the triggers of axon The CMT Neuropathy Score (CMTNS) balance and mobility.
degeneration. We are currently testing and the Examination Score Biomarkers used in the CMT1X study
the applicability of this approach in (CMTES)—These measures are based will include:
multiple models of CMT, collaborating on patients’ symptoms, physical MRI, the assessment of muscle, has
with a number of companies to show findings and electrophysiology. been shown to a sensitive measure of
that candidate drugs can promote Measures include assessment of progression in CMT1A, and this will be
axon survival, preserve nerve function sensory symptoms as well as motor extended to CMT1X.
and prolong patient mobility in skills and strength of the arms, hands
demyelinating Type 1 CMT disorders. and legs. Skin Biopsies—Research shows that
CMT affects expression of genes in
We are supporting work done by The CMT Health Index the nerves found in skin, which can
Dr. Maurizio D’Antonio of the San (CMT-HI)—This is a patient-reported be used to measure response to
Raffaele Scientific Institute to test new measure to assess therapeutic benefit treatment.
drug classes for CMT1B, which are in CMT clinical trials, but it may also
being developed for stress-related be used to measure overall CMT Neurofilament Light Chain—
disorders such as stroke, Alzheimer’s patient health. This measure is unique Blood plasma levels of the protein
and retinal degeneration. because it measures patients’ neurofilament light chain have been
shown to be a marker of axonal
perspectives on their mobility, foot
The CMTA has just approved two and ankle strength, hand and finger damage as levels are elevated in CMT
new projects to test small molecule function, and a series of related patients and correlate with disease
therapies in preclinical models of symptoms (pain, fatigue, numbness, severity.
CMT1A. hearing, etc.).
Most recently, the Board of Directors
awarded the Feltri/Wrabetz Lab at
the University at Buffalo $138,110 for
a 12-month study that will test whether
drugs already approved for
hypertension and erectile dysfunction
can stifle the unfolded protein
response of CMT1B.

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