Drug discovery programs

Ubiquitin-competing molecules (UCM)

UCM are drug-like small molecules tailored to bind frataxin and effectively prevent frataxin ubiquitination and degradation. Reduced frataxin degradation leads to higher levels of bioavailable cellular frataxin and improved cellular metabolism in cells derived from Friedreich ataxia patients. (US patent 8,703,749)

Rufini A, Cavallo F, Condò I, Fortuni S, De Martino G, Incani O, Di Venere A, Benini M, Massaro DS, Arcuri G, Serio D, Malisan F, Testi R. 2015. Highly specific ubiquitin-competing molecules effectively promote frataxin accumulation and partly rescue the aconitase defect in Friedreich ataxia cells. Neurobiol Dis. Mar,75 :91-9. Epub 2014 Dec 27.

Long-lasting frataxin (LLF)

LLF is recombinant human frataxin engineered to be resistant to proteasome degradation, and displaying enhanced half-life in living cells. It is currently being validated for protein-delivery therapeutic approaches in Friedreich ataxia cellular models. (US patents 9,217,019 and 9,944,906 and EU Patent 2,598,525)

Rufini A, Fortuni S, Arcuri G, Condò I, Serio D, Incani O, Malisan F, Ventura N, Testi R. 2011. Preventing the ubiquitin/proteasome-dependent degradation of frataxin, the protein defective in Friedreich’s Ataxia. Hum Mol Genet. Apr 1;20(7):1253-61. Epub 2011 Jan 7.