Toward Development of A Cure
Rare Disease Facts
Over 7,000 different rare diseases are know today, with more being discovered each day; 30 million people in the United States are living with a rare disease. This equates to 1 in 10 Americans or 10% of the U.S. Population.
Majority (80%) of rare diseases are genetic in origin, and thus are present throughout a person’s life, even if symptoms do not immediately appear. Approximately 50% of rare diseases do not have a disease specific foundation supporting or researching their rare disease.
95% of all rare diseases do not have a single FDA approved treatment.
AGU and Drug Development Process
Every new treatment follows FDA approval process, where a drug is determined to provide benefits that outweigh its known and potential risks for the intended population. To determine the benefits and risks of a drug/treatment, a researcher investigates effects of the drug, drug delivery and doses in animals before submitting an application to try the treatment in humans. It is Investigational New Drug (IND) application and FDA approval allows to give the new drug in patients.
We've been funding two different treatments for Aspartylglucosaminuria since 2013: Chaperone Therapy and Gene Replacement Therapy. Both drug developments go through the same development process. Chaperone therapy uses already existing medicines to treat a new disease (AGU), hence after testing it in a patient's cultured cells, governing authority allowed it to progress into a clinical trial. Gene replacement therapy went through several years of a rigorous pre-clinical animal testing to prove efficacy and safety of the chosen formulation of the gene therapy medicine. The results of this study was published in 2021.
Since then we
Manufactured gene therapy drug (AGA gene + delivery vector);
Conducted drug clearance testing and received CoA for the drug.
We are currently (our progress is indicated with the orange arrow on the chart above):
Conducting toxicology, dose determination and biodistribution study;
Putting together the paperwork to submit results for the above to FDA for IND (Investigational New Drug) Application;
and plan to start clinical trials in AGU patients right after the FDA approval.
Published Research Funded by Rare Trait
Melanie Meister and Ritva Tikkanen (2014) Endocytic Trafficking of Membrane-Bound Cargo: A Flotillin Point of View. Membranes 2014, 4(3), 356-371. https://doi.org/10.3390/membranes4030356
Banning, A., Gülec, C., Rouvinen, J. et al. Identification of Small Molecule Compounds for Pharmacological Chaperone Therapy of Aspartylglucosaminuria. Sci Rep 6, 37583 (2016). https://doi.org/10.1038/srep37583
Banning, A.; König, J.F.; Gray, S.J.; Tikkanen, R. Functional Analysis of the Ser149/Thr149 Variants of Human Aspartylglucosaminidase and Optimization of the Coding Sequence for Protein Production. Int. J. Mol. Sci. 2017, 18, 706. https://doi.org/10.3390/ijms18040706
Antje Banning, Manuel Schiff, Ritva Tikkanen (2018), Amlexanox provides a potential therapy for nonsense mutations in the lysosomal storage disorder Aspartylglucosaminuria. Biochimica et Biophysica Acta, 1864:668-675. https://doi.org/10.1016/j.bbadis.2017.12.014
Goodspeed, K., Harder, L., Hughes, S., Conger, D., Taravella, J., Gray, S.J. and Minassian, B. (2018), Optical coherence tomography features in brothers with aspartylglucosaminuria. Ann Clin Transl Neurol, 5: 1622-1626. https://doi.org/10.1002/acn3.672
A. Tokola, M. Laine, R. Tikkanen and T. Autti (2019), Susceptibility-Weighted Imaging Findings in Aspartylglucosaminuria. American Journal of Neuroradiology Nov 2019, 40 (11) 1850-1854. https://doi.org/10.3174/ajnr.A6288
Xin Chen, Sarah Snanoudj-Verber, Laura Pollard, Yuhui Hu, Sara S. Cathey, Ritva Tikkanen, Steven J. Gray, Pre-clinical Gene Therapy with AAV9/AGA in Aspartylglucosaminuria Mice Provides Evidence for Clinical Translation, Molecular Therapy, Volume 29, Issue 3, 2021, Pages 989-1000, https://doi.org/10.1016/j.ymthe.2020.11.012.