According to an article in BioSpace, Dyne Therapeutics has recently announced data from preclinical trials of its FORCE platform. This program is aimed at creating treatments for myotonic dystrophy type 1 (DM1). Researchers are excited by the positive data; it shows that their therapy reduces toxic DMPK RNA.
About Myotonic Dystrophy
Myotonic dystrophy is a form of muscular dystrophy that is characterized by the progressive weakening and atrophy of the muscles. There are two forms of this condition: type 1 and type 2, with the latter often resulting in less severe symptoms and affecting different muscles. Type 1 is the result of a mutated DMPK gene, while type 2 occurs due to a mutated ZNF9 gene. Common symptoms of both forms include an abnormal heart rhythm, weakness of the cardiac muscles, problems with breathing, weakness in the voluntary muscles, cataracts, learning disabilities, an inability to relax the muscles, issues swallowing, gallstones, constipation, abnormal uterus muscles, and issues with speech, vision, and hearing. There is currently no cure or treatment specific to myotonic dystrophy; treatment is symptomatic.
About the FORCE Platform
This program utilizes transferrin 1 receptor, TfR1, which plays an important role within muscle cells. This receptor sits on the surface of cells, and its job is to transport iron into them. Using fragment antibodies that bind to TfR1, researchers are able to attach therapeutic payloads.
The lead candidate within this program is a fragment antibody connected to an antisense oligonucleotide (ASO). Using the antibody, researchers are able to target muscle tissue. Once the therapy reaches the tissue, it decreases the amount of toxic DMPK RNA within the nucleus. Splicing proteins are then released, followed by the processing of normal mRNA and proper translation of proteins. If successful, this therapy has the potential to stop and even reverse disease progression.
Preclinical Data
Previous data has demonstrated that this therapy is able to significantly reduce cytoplasmic wild type DMPK RNA in mouse models that express the human version of TfR1. In order to better assess how the treatment would act in humans, researchers created a mouse model that expresses both human TfR1 and a human DMPK gene with severe mutations for DM1. They went on to dose the mice with two doses of the leading candidate in the FORCE program.
Their results included:
- After 14 days, the toxic DMPK was reduced by
- 60% in the heart
- 56% in the diaphragm
- 54% in the tibialis anterior
- 39% in the gastrocnemius
- The therapy was well tolerated
Previous research has shown that a 30-50% reduction of toxic DMPK is disease modifying, meaning that this treatment holds potential. Researchers plan to further develop and improve this candidate with the hope that it moves on to human trials.
According to the president and chief executive officer of Dyne Therapeutics, they plan to submit three Investigational New Drug applications for the three drug candidates in their program. If all goes according to plan, they will be sent to the FDA between the final quarter of 2021 and the final quarter of 2022.
