Multinational, randomized, placebo-controlled, double-blinded, cross-over Phase III clinical trial to assess safety and efficacy of ALL (IB1001) versus Placebo for the treatment of NPC.
Acetyl-DL-leucine (ADLL) has been used for more than 6 decades in France to treat acute vertiginous episodes. The clinical experience has shown that it is a well-tolerated drug without serious adverse events. In 2015, our pilot case-series study in patients with Niemann-Pick disease, type C ( NPC) indicated the possible positive symptomatic effects on cerebellar ataxia, but also other modalities of this rare debilitating disease. The further basic research studies, and clinical trials demonstrated the positive effects of acetyl-L-leucine (ALL) in lysosomal storage disorders, suggesting not only symptomatic, but also disease-modifying effects. I am the principal investigator of the only study site in Switzerland for the multinational, randomized, placebo-controlled, double-blinded, cross-over Phase III study that will assess the safety and efficacy of ALL (IB1001) versus Placebo for the treatment of children >4 years of age and adults with NPC. The development of this re-purposed drug for lysosomal storage diseases is a model example of the translational and back-translational research enabled by the close cooperation with the lab of Prof. Frances Platt, University of Oxford.
Bremova-Ertl T, Claassen J, Foltan T, Gissen P, Hahn A, Hassan A, Hennig A, Jones S, Kolnikova M, Martakis K, Ramaswami U, Sharma R, Schneider S Efficacy and Safety of N-acetyl-L-leucine in Niemann-Pick disease type C. J Neurol 2021 Aug 13;1-12. doi: 10.1007/s00415-021-10717-0. Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C - PubMed (nih.gov)
Kaya E, Smith D, Smith C, Morris L, Bremova-Ertl T, Cortina-Borja M, Fineran P, Morten K, Poulton J, Spencer J, Strupp M and Platt F Acetyl-leucine slows disease progression in lysosomal storage disorders. Brain Communications, Volume 3, Issue 1, 2021, fcaa148, https://doi.org/10.1093/braincomms/fcaa148. LINK: Acetyl-leucine slows disease progression in lysosomal storage disorders - PubMed (nih.gov)
Churchill GC, Strupp M, Factor C, Bremova-Ertl T, Factor M, Patterson MC, Platt FM, Galione A. Acetylation turns leucine into a drug by membrane transporter switching. Sci Rep. 2021 Aug 4;11(1):15812. doi: 10.1038/s41598-021-95255-5. Acetylation turns leucine into a drug by membrane transporter switching - PubMed (nih.gov)
Bremova T, Malinová V, Amraoui Y, Mengel E, Reinke J, Kolníková M, Strupp M. Acetyl-dl-leucine in Niemann-Pick type C: A case series. Neurology. 2015 Oct 20;85(16):1368-75. doi: 10.1212/WNL.0000000000002041. Acetyl-dl-leucine in Niemann-Pick type C: A case series - PubMed (nih.gov)
Platt Lab (ox.ac.uk)
Intrabio – biopharmaceutical research and development