Page 4 - 2020 Summer CMTA Report

University of Miami Researchers

Find New CMT Type That May Be

Treatable with Diabetes Drugs

niversity of Miami recessive form of the disease.
researchers led by Dr. Züchner and his colleagues
Dr. Stephan Züchner are looking to screen undiagnosed
have discovered a new CMT patients to identify as many
type of CMT that may patients as possible in preparation
be treatable with the for clinical trials.
Usame drugs used to “We’re very optimistic about
reduce elevated sorbitol in people the therapy going forward,”
with diabetes. Dr. Züchner said, noting that the
The initial discovery was drug basically cured CMT in fruit
made by Andrea Cortese, MD, flies. “This is a remarkable discov-
and Adriana Rebelo, PhD, who ery only possible due to large scale
worked with a large group of genomic data aggregation from
CMT2 families convened by the volunteering CMT patients,” he
Inherited Neuropathy Consor- added.
tium, with support from the Dr. Züchner, MD, PhD, is Dr. Stephan Züchner
National Institutes of Health, the a professor of human genetics
CMTA and many others. and neurology and chair of the researchers use. Using a different
The newly discovered type is Dr. John T. Macdonald Founda- strategy, the researchers found the
caused by a mutated SORD (sor- tion Department of Human relevant variations hidden behind
bitol dehydrogenase) gene that Genetics at the University of a “pseudogene.” Pseudogenes mir-
raises sorbitol levels so high they Miami Miller School of Medicine. ror the DNA sequence of their
cause nerve damage. Researchers He is also a member of the active counterparts, but have no
found that treating fruit flies with CMTA’s STAR Advisory Board. function.
a diabetes drug (aldose reductase He and his team—Rebelo, associ- After identifying the gene, the
inhibitors) reduced their high lev- ate scientist at the Hussman team identified 45 individuals from
els of sorbitol to near normal. Institute for Human Genomics, 38 families who had the specific
An estimated 3,000–5,000 and Cortese, a visiting scholar mutation. With gene and patients
people in the United States—and from University College of Lon- identified, the next step was finding
more than 60,000 worldwide— don—discovered the SORD the necessary animal model.
may have this type of CMT, mutation “hidden” from the gene Serendipity intervened in the
making it the most common analysis software that most person of R. Grace Zhai, PhD,
senior associate dean for basic
science research and associate
Readers interested in being screened for the new type should fill out a professor in the Department of
Patients as Partners in Research profile. The criteria for screening are: Molecular and Cellular Pharma-
1) you have received a diagnosis of CMT, but genetic testing did not cology at the Miller School. Her
reveal with certainty the responsible gene; lab is right across the street from
2) your parents never had CMT symptoms. Dr. Züchner’s and the two of
(continued on page 6)

This piece was adapted from an article by Damian McNamara in Inventum, published by the University of Miami Miller
School of Medicine. The full article is available at physician-news.umiamihealth.org/innovative-genetic-research-may-lead-to-
treatment-for-inherited-form-of-peripheral-neuropathy/.

4 THE CMTA REPORT SUMMER 2020