DTx Pharma Receives NIH Funding to Advance RNA-based Therapies for CMT

The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health (NIH), has awarded DTx Pharma a funding grant to advance development of promising new therapeutic candidates for Charcot-Marie-Tooth (CMT) type 1A (CMT1A) disease.

The therapeutic candidates are specially designed RNA oligonucleotide molecules that aim to lower PMP22 levels and restore normal functions in cells that are affected in CMT1A disease.

In preclinical studies funded in large part by the CMT Research Foundation, DTx Pharma already has discovered several new molecules that reduce PMP22 in cultured cells and have the potential to treat this condition.

The findings from those studies provided the basis for the recent grant application. To date, DTx Pharma has earned a total of $2 million in funding grants to advance its RNA-based therapies, which also include treatments for eye diseases and neurological diseases, such as Alzheimer’s.

“The CMT Research Foundation and the NIH have supported ground-breaking research for rare diseases like CMT and we are pleased to continue to partner with organizations that share our commitment to developing therapies where none exist,” Arthur T. Suckow, PhD, CEO of DTx Pharma, said in a press release.

“With this non-dilutive funding and support from our partners, we are well-positioned to develop a clinical candidate for CMT1A that is effective at suppressing the disease-driving gene, PMP22,” Suckow said.

CMT1A, the most common form of CMT disease, is caused by a duplication of the PMP22 gene that causes cells to produce too much of a protein with the same name, PMP22.

This protein is necessary for forming the myelin sheath, a protective coating of nerve cells that help them transmit electrical signals throughout the body. But excess PMP22 causes defects in the myelin sheath, leading to impaired nerve cell signaling, and causing the weakness and deterioration of muscle tissue that is observed in people with CMT1A.

DTx is developing specific RNA molecules, called short interfering RNAs, that help reduce PMP22 production in nerve cells, restoring the normal myelin sheath and nerve cell functioning.

These small RNA molecules are designed with a particular sequence so that they bind and trigger the elimination of PMP22’s messenger RNA — an intermediate molecule generated from DNA that works as a template for protein production — preventing more protein from being generated.

While RNA medicines have been impaired historically by problems in their delivery to cells of interest and by rapid clearance from the body, DTx uses its proprietary FALCON technology to address those issues.

Essentially, the approach conjugates RNA therapeutic molecules with long chains of fatty molecules that, in addition to making the RNAs more stable and durable, have high affinity to specific tissues or cells.

So far, the approach has enabled the delivery of therapeutic RNAs specifically to cells of the retina, muscle, heart, neurons, and specialized cells of the immune system.

“We invested in DTx’s technology because of its potential to be groundbreaking for CMT, and in a very short period, DTx has generated significant success,” said Susan Ruediger, CMT Research Foundation’s CEO.

“This partnership exemplifies how a relatively small investment from the CMT Research Foundation can lead to a significant follow-on capital for a promising project to develop treatments for CMT. This wouldn’t have happened without the CMTRF’s early investment,” Ruediger added.