The inventors have developed two novel and complementary approaches for the treatment of MLD: The first approach is based on the natural products Epicoccolid B and Epipyrone, which are derived from the mold fungus Epicoccum nigrum. These compounds inhibit the cerebroside-sulfotransferase, which is an enzyme that generates sulfatide. Thereby, the sulfatide concentration is lowered.
In addition (second approach) the researchers have exchanged certain amino acids of human ASA resulting in a much higher enzymatic activity. Previous clinical studies have demonstrated the feasibility of enzyme compensation therapy for treating MLD. However, it became clear that large amounts of enzyme need to be administered thereby potentially causing significant side-effects. These problems are overcome by the present approach.
The aforementioned compounds as well as the mutated enzyme are offered for licensing.
- Novel and complementary approach for treating MLD
- Demonstrated proof of concept
The researcher have generated mouse models for MLD and have validated efficacy of their therapeutics. European patent priority applications have been field for both approaches.
Schuster, T., et al. (2017) Potential of surfactant-coated nanoparticles to improve brain delivery of arylsulfatase A. J Control Release, S0168-3659(17)30079-2.
Doerr, J., et al. (2015) Arylsulfatase A overexpressing human iPSC-derived neural cells reduce CNS sulfatide storage in a mouse model of metachromatic leukodystrophy. Mol Ther 23:1519-31.