Why Is Design Therapeutics Stock Moving Lower Today?

Aug. 15, 2023, Design Therapeutics planned to reformulate its Friedreich ataxia drug following injection site reactions in a Phase 1 study. The company plans to begin a new multiple-dose Phase 1 study in the second half of 2024, with initial data in the first half of 2025. Based on current methods and procedures, the treatment effect of DT-216 on FXN protein was inconclusive due to high intra-individual variability, consistent with what was seen in the observational study.

Rationale and protocol of a double-blind, randomized, placebo-controlled trial to test the efficacy, safety and tolerability of Dimethyl Fumarate in Friedreich Ataxia (DMF-FA-201)

Chiara Pane1, Alberto M. Marra, Ludovica Aliberti, Mario Campanile, Federica Coscetta, Giulia Crisci, Roberta D'Assante, Angela Marsili, Giorgia Puorro, Andrea Salzano, Antonio Cittadini, Francesco Saccà; Rationale and protocol of a double-blind, randomized, placebo-controlled trial to test the efficacy, safety and tolerability of Dimethyl Fumarate in Friedreich Ataxia (DMF-FA-201). Front. Neurosci. Sec. Neuropharmacology, Volume 17 - 2023 | doi: 10.3389/fnins.2023.1260977 

 Conclusions: this is the first study aimed at exploring the ability of DMF, an already available treatment for MS and psoriasis, to correct the biological deficits of FRDA and potentially improve mitochondrial respiration in-vivo.

Interferon Gamma Enhances Cytoprotective Pathways via Nrf2 and MnSOD Induction in Friedreich’s Ataxia Cells

Luffarelli, R.; Panarello, L.; Quatrana, A.; Tiano, F.; Fortuni, S.; Rufini, A.; Malisan, F.; Testi, R.; Condò, I. Interferon Gamma Enhances Cytoprotective Pathways via Nrf2 and MnSOD Induction in Friedreich’s Ataxia Cells. Int. J. Mol. Sci. 2023, 24, 12687. doi:10.3390/ijms241612687 

The cytokine interferon gamma (IFN-γ) has been shown to increase frataxin expression in FRDA cells and to improve functional deficits in FRDA mice. Currently, IFN-γ represents a potential therapy under clinical evaluation in FRDA patients. Here, we show that IFN-γ induces a rapid expression of Nrf2 and MnSOD in different cell types, including FRDA patient-derived fibroblasts. Our data indicate that IFN-γ signals two separate pathways to enhance Nrf2 and MnSOD levels in FRDA fibroblasts. MnSOD expression increased through an early transcriptional regulation, whereas the levels of Nrf2 are induced by a post-transcriptional mechanism. We demonstrate that the treatment of FRDA fibroblasts with IFN-γ stimulates a non-canonical Nrf2 activation pathway through p21 and potentiates antioxidant responses under exposure to hydrogen peroxide. Moreover, IFN-γ significantly reduced the sensitivity to hydrogen peroxide-induced cell death in FRDA fibroblasts. Collectively, these results indicate the presence of multiple pathways triggered by IFN-γ with therapeutic relevance to FRDA.