New Friedreich’s ataxia therapy may be set for clinical trials by 2025
Design Therapeutics reworked DT-216 formulation after Phase 1 test problems
Design Therapeutics is on track to start clinical trials next year of its new and improved experimental treatment for Friedreich’s ataxia (FA), called DT-216P2.
“Leading our portfolio of potential first- or best-in-class therapies is DT-216P2 for FA, a serious neurodegenerative disease with a significant need for new therapies, and we remain on track to start patient trials in 2025,” Pratik Shah, PhD, Design’s chairperson and CEO, said in a company press release.
FA is caused by mutations in the gene FXN, which provides instructions to make frataxin, a protein essential for mitochondria, the so-called powerhouses of cells that are vital for energy production. Without functional frataxin, patients’ cells cannot generate energy efficiently, which leads to the cellular dysfunction that drives disease symptoms.
In most cases, FA is caused by a type of mutation called a GAA trinucleotide repeat expansion. In the FXN gene, there’s a region where three building blocks of DNA, called nucleotides — specifically one guanine (G) and two adenines (AA) — are sequentially repeated about five to 33 times. In FA, these nucleotides are repeated dozens or even hundreds of times. The excessive repeats “turn off” the FXN gene, preventing frataxin from being produced.
Turning FXN gene back on
Design has been pioneering an approach for FA treatment using molecules called GeneTACs that can bind to the GAA repeat expansion and, at the same time, pull in parts of the molecular machinery that cells use to make protein. The aim is to “turn on” the faulty FXN gene, restoring frataxin production to combat FA symptoms and slow the disease’s progression.
“Our strategy is to address the disease’s root cause by increasing endogenous frataxin levels,” Shah said.
Design had been developing a FA-specific GeneTAC molecule dubbed DT-216 that would have been injected into the bloodstream. Data from Phase 1 studies suggested the treatment was activating the FXN gene as intended, but patients developed injection reactions to some ingredients in the formulation, prompting Design to rework the therapy.
The new formulation is expected to function like the previous one, but without the injection reactions. Design said it expects to conclude good-laboratory-practice studies of DT-216P2 by the end of this year and hopes to start testing it in people in 2025.
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