Although there are more than 100 different genes that cause CMT, there are some common symptoms that affect people living with CMT such as axon degeneration, muscle loss, and more. Part of the CMTA’s strategy is to look at therapeutic approaches that could potentially help several or many different types of CMT. Below you will find some information on projects we are funding that span across several types of CMT including those not yet to have a gene associated. You will also find some information on our approach to funding work across different therapy areas from gene therapy, to small molecules, and preparing for trials.
PROJECT GOAL: TESTING HDAC6 INHIBITORS
Grant Amount: $44,507
Principal Investigator: Robert Burgess, PhD, The Jackson Laboratory
Dr. Robert Burgess, a member of the CMTA’s Scientific Advisory Board, is using mouse models of several forms of CMT to determine which types may be candidates for treatment with HDAC6 inhibitors and whether HDAC6 inhibitors may be of therapeutic benefit across a variety of CMT types.
PROJECT GOAL: INHIBITION OF SARM1 IN CMT TYPES 1A, 1X, 2E, 2D AND 2S
Grant Amount: $110,000
Principal Investigator: Robert Burgess, PhD, The Jackson Laboratory
Dr. Burgess will conduct tests to determine whether inhibiting SARM1 is of therapeutic benefit in multiple forms of CMT. If this is successful, the approach could potentially be applied to other types of CMT.
PROJECT GOAL: GENE DISCOVERY PROJECT
Grant Amount: $300,000
Principal Investigator: Stephan Züchner, MD, PhD, University of Miami
To share data, curate existing data, and develop a web-based access for CMT patients to genomic studies; implement and validate a machine learning algorithm for CMT genetic variation; improve genetic annotation in GENESIS; and implement repeat expansion detection in CMT and advanced structural variant detection.
“The work in Züchner’s lab aligns perfectly with the CMTA’s Strategy to Accelerate Research (STAR),” CMTA CEO Amy Gray said. “Funding this project is another way the CMTA supports the development of therapies for the CMT community,” she added, explaining, “As we discover more of the genetic causes of the unidentified forms of CMT, we can strategically target them with potential therapies.”
Züchner and the team of University of Miami and INC researchers use purpose-developed software, the GENESIS platform, to perform large-scale exome and genome analysis on the DNA of patients with CMT2 (among others), which primarily affects the axons of motor and sensory neurons. Up to half of all individuals with CMT have CMT2, or approximately 1 in 5,000 people.
Dr. Züchner’s study, designated as Project #6602 by the Inherited Neuropathy Consortium (INC), is an ongoing study currently in its tenth year to identify new causes of CMT for those who cannot find the genetic cause of their CMT with tests that are currently available.
Individuals who have already been seen at one of the INC sites who are eligible for this project have probably already been enrolled, but they can contact their INC site directly if they have questions about participation. As a new patient, to be eligible for this project, you first need to contact one of the INC locations to be evaluated and enroll in the INC Natural History Study (Project #6601). This will involve being seen in person at one of the INC’s sites.
To learn how to enroll in Project #6601, please visit www.rarediseasesnetwork.org/cms/inc/6601.
Once you’ve participated in Project #6601, you may proceed with Project #6602. Instructions for enrolling in Project #6602 can be found here: www.rarediseasesnetwork.org/cms/inc/6602.
DRUG DEVELOPMENT EFFORTS
The progression of all types of CMT occurs as the longest axons are compromised in a process called axon degeneration. We are working with partners to develop molecules that regulate of the triggers of axon degeneration. We are currently testing the applicability of this approach in multiple models of CMT, collaborating with a number of companies to show that candidate drugs can promote axon survival, preserve nerve function and prolong patient mobility in demyelinating Type 1 CMT disorders.
GENE THERAPY
The CMTA looks forward to a time when doctors are able to use genetic therapies to treat the root cause of CMT rather than prescribing medications or recommending surgery. We are already envisioning the possibilities that gene therapy holds for our community of 3 million people worldwide living with CMT. In fact, we’re leading the pursuit to explore gene therapy in CMT by expanding our Strategy to Accelerate Research (STAR) program and our STAR Advisory Board.
In CMT, the genetic causes for many types of CMT are already known, which allows scientists to more efficiently zero in on genetic solutions to treat—and possibly cure—the disease. As we continue gene therapy research inside the lab, our ultimate goal is to transform it into effective treatments for people living with CMT.
Given the increased feasibility and applicability of gene therapy to CMT, the CMTA is investing in a number of gene therapy efforts to help bring treatments to patients.
PREPARING FOR CLINICAL TRIALS
In partnership with the Inherited Neuropathy Consortium, we are building on their recent successes in development of novel biomarkers and outcome measures in CMT1A and supporting major efforts to extend development and testing of critical biomarkers for CMT1B, CMT1X, and 2A to support upcoming clinical trials.
UNDIAGNOSED TYPE 2
Approximately 50 percent of CMT2 patients do not yet have a definitive genetic diagnosis. Dr. Stephan Züchner at the University of Miami is working to change that, spearheading an ambitious project to identify new disease-causing mutations in patients seen in the Inherited Neuropathy Consortium (INC).