"Dune"-inspired Arrakis Therapeutics has tested its spice—an RNA-targeting small molecule—in a mouse model of myotonic dystrophy type 1 (DM1), with the drug reversing the prolonged muscle contraction that is characteristic of the disease.
Arrakis, based not on a desert planet but in Waltham, Massachusetts, presented the results at the Cell Symposia: Chemical biology in drugging the undrugged conference in San Francisco on Dec. 4, according to a release.
Patients with DM1 have copies of the DMPK gene that produce mRNA with repeated CUG nucleotide sequences; this errant mRNA disrupts the work of RNA-processing proteins, leading to symptoms such as muscle wasting, cardiac dysfunction, cognitive impairment and the characteristic myotonia, which is an inability for muscles to relax after contracting.
Arrakis’ small molecule binds to the repeated CUG sequences and neutralizes them, the company said in the release, and was able to restore normal RNA splicing in muscle cells derived from patients.
“While there have been serendipitous discoveries of small molecule drugs that bind to RNA, we believe this is one of the clearest examples of a rationally designed small molecule that has been purpose-built to address an RNA disease target” Arrakis CEO Michael Gilman, Ph.D., said in the release. “We believe that our DM1 program is the first of many potential RNA-targeted small molecule drug candidates that will emerge from our platform in coming years.”
DM1 is the most common form of myotonic dystrophy, estimated to affect about one in every 8,000 people. DM1 has no cure, with treatments instead focused on managing symptoms.
Much like its namesake fictional planet, Arrakis has attracted extensive attention for its drugs in its nine-year history, though the company has eschewed potential pharma suitors in the past. The firm teamed up with Roche for a $190 million upfront deal in 2020 after raising a $75 million series B the previous year.