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Targeting SREBP Regulation for CMT1A

With CMTA support of $74,000, researchers at the University of Wisconsin-Madison, led by CMTA Strategy To Accelerate Research (CMTA-STAR) Advisory Board Chairperson, John Svaren, PhD, studied whether a fat-based compound could help lower the levels of PMP22, the gene that causes CMT1A when too much of it is made. 

CMT1A is caused by having an extra copy of the PMP22 gene, which leads to too much PMP22 protein in Schwann cells. These are the cells responsible for creating and maintaining peripheral nerve myelin, the protective covering around peripheral nerves. When PMP22 levels are too high, myelin does not work properly, which disrupts nerve signals and leads to symptoms of CMT. Earlier CMTA-supported research from Dr. Svaren showed that reducing PMP22 levels in Schwann cells can improve symptoms in a model of CMT1A. 

In this follow-up study, the team tested whether a modified form of a natural fat could reach peripheral nerves and reduce PMP22 levels. The compound did reach the nerve tissue, which is an important step forward, but it did not produce a clear improvement at the dose used. The researchers also built new tools that will support future CMT1A studies, including a more accurate method to measure PMP22 and a way to study how nerve lipids change during treatment. 

While the study did not lead to a new therapy, it provided valuable information and opened the door to improved strategies for targeting PMP22 in future research.

John Svaren, PhD, with a microscope in his laboratory.

Principal Investigator

John Svaren, PhD
University of Wisconsin-Madison

Therapy / Approach

Small Molecule / Target Validation

Project Duration

1 Years

Total CMTA-STAR Project Investment

$73,756

Completed