What is CMT-SORD?
CMT-SORD, also known as Sorbitol Dehydrogenase Deficiency, is a recently discovered, unique type of Charcot-Marie-Tooth disease (CMT). Identified in May 2020 with funding from CMTA, this type of CMT is caused by mutations in the SORD gene. These mutations lead to the buildup of a sugar alcohol called sorbitol, which becomes toxic to the nerves as it accumulates in the body. This toxicity results in CMT-SORD symptoms, including muscle weakness and sensory loss.
How is SORD related to CMT?
CMT-SORD, also known as Sorbitol Dehydrogenase Deficiency (SORD Deficiency), is an axonal type of CMT, meaning it primarily affects the part of the nerve responsible for transmitting signals (the axon). Many individuals with CMT-SORD were initially diagnosed with CMT Type 2 (CMT2) or distal hereditary motor neuropathy (dHMN, aka HMN), as these are also axonal types of CMT. Doctors often report symptoms commonly seen in other types, with severity ranging from person to person.
How is CMT-SORD diagnosed?
Diagnosing CMT-SORD involves the following steps:
- Clinical evaluation: A doctor assesses for muscle weakness, impaired mobility, and other CMT-SORD symptoms.
- Sorbitol measurement: Elevated levels of sorbitol in blood or urine are indicative of SORD deficiency.
- Genetic testing: Genetic testing for CMT-SORD can identify mutations in the SORD gene.
Can I Have CMT-SORD if Nobody Else in My Family Has CMT?
Yes, you can have CMT-SORD even if no one else in your family has CMT. CMT-SORD is inherited in an autosomal recessive manner, meaning both parents must carry the mutated gene for a child to inherit the disease. Since carriers do not show any CMT symptoms and do not have CMT, people with CMT-SORD are usually the first ones in their family with CMT.
Can I Pass CMT-SORD to My Children?
Since CMT-SORD is inherited in an autosomal recessive manner, both parents must carry a copy of the mutated SORD gene for a child to inherit the disease. If you have CMT-SORD, your children will inherit one copy of the SORD gene mutation, making them carriers. However, they will not have CMT-SORD unless your partner is also a carrier of the mutated SORD gene and passes theirs onto the children, too. If both parents are carriers, there is a 25% chance that the child will inherit CMT-SORD with each pregnancy.
How is CMT-SORD Treated
Treating CMT-SORD focuses on individualized symptom management. While there is no FDA-approved treatment for CMT-SORD yet, many symptoms can be effectively managed. Common approaches include:
- Physical and occupational therapy
- Foot and ankle orthoses (AFOs)
- Staying as active as possible
- Surgery to correct foot deformities
Being seen at one of CMTA’s Centers of Excellence is one of the best ways to manage CMT-SORD. These centers are staffed by expert CMT physicians, clinicians, and researchers who provide comprehensive care for individuals affected by CMT. Visit our Centers of Excellence page to find the nearest location.
Ongoing Research and Potential Treatments for CMT-SORD
Although there is no FDA-approved treatment for CMT-SORD, research is advancing rapidly. CMTA-STAR Alliance Partner Applied Therapeutics is conducting the ongoing Phase III INSPIRE trial for govorestat (AT-007), a potential treatment for CMT-SORD. This experimental medication has shown promise in lowering sorbitol levels, addressing the underlying cause of CMT-SORD symptoms and disease progression.
CMTA’s Role in Advancing CMT-SORD Research
The discovery of the SORD gene mutation that causes CMT-SORD marked a monumental moment in CMT research. Funded by CMTA, this discovery offered a clear therapeutic pathway for this previously unidentified type of CMT. CMTA’s Strategy to Accelerate Research (STAR) program immediately accelerated the research.
Collaborating with the Inherited Neuropathy Consortium (INC) and other research partners, CMTA-STAR had already developed essential clinical trial readiness tools. These include the CMT Functional Outcomes Measure (CMT-FOM), which tells if a treatment is working, and the CMT Health Index (CMT-HI), which evaluates how a patient “feels.” The Patients as Partners in Research platform made rapid trial recruitment possible by connecting scientists with patients who possibly had CMT-SORD and wanted to participate in CMT research.
These combined efforts took CMT-SORD from discovery to a Phase III clinical trial in just two years—an unprecedented achievement. CMTA continues to ensure that all clinical trial readiness tools are in place so that trials can again begin without delay when the CMT science is ready.
Hope for the Future
The rapid progress in CMT-SORD research provides hope for those with this unique type of CMT and the entire CMT community. If govorestat (AT-007) is approved, it will be the first-ever treatment for any form of CMT, setting the stage for future therapies.
CMTA remains committed to accelerating research and ensuring that breakthroughs like CMT-SORD lead to life-changing treatments.
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Page updated: October 30, 2024