Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease due to CAG expansion in the huntingtin gene. Through a screening on polyQ-hHTT aggregation in HeLa cells, F. Maschat (CNRS Montpellier) recently identified an inhibitory 23aa peptide (P42) lying within human HTT that specifically acts on HD and prevents the aggregation process. To improve the systemic delivery of P42 through a non-invasive method of administration, a new strategy has been developed combining the properties of the cell penetrating peptide TAT with our water-in-oil microemulsion AONYS® allowing per mucosal delivery of P42 to the CNS.
The protective properties of P42 have been confirmed on different polyQ-hHtt-induced phenotypes in the HD Drosophila model (Maschat et al.). We further evaluated the therapeutic potential of P42 in the R6/2 HD mouse model. Our studies demonstrated an unprecedented protective effect of P42, in both pre- and post-symptomatic treatments, and highlight a new therapeutic strategy for HD, associating an efficient peptide with the powerful delivery technology AONYS® (see Arribat et al. 2014). This work is being continued in collaboration with Dr Florence Maschat et Dr Edwin Chan).