Gene Replacement Therapy (GRT)
In several studies various viruses were used to deliver a healthy gene to AGU mice either to the liver (by intravenous injection) or the brain (by direct injection into the brain). In all cases, the transferred AGA gene successfully produced the enzyme and the cells with the new gene were cleared from the toxic storage material. In addition, the targeted cells shared the AGA enzyme with their neighbors creating a larger area of therapeutic effect. These studies were encouraging and showed that gene therapy could work.
Rare Trait Swiss is a Swiss non-profit association, founded in March 2021 by the parents of a child affected by a rare lysosomal storage disease called aspartylglucosaminuria (AGU). AGU is a progressive degenerative disease that kills affected children as early as adulthood. There are only about 200 known cases of this disease worldwide.
Rare Trait Swiss is an independent, non-political association whose nature is to work for: the charity of patients with Aspartylglucosaminuria (AGU), information for families of patients and healthcare professionals who want to know more about (AGU).
Aspartylglucosaminuria (AGU) is a rare lysosomal disease, it is now well understood and it’s cure is well known, the only thing remaining to start the clinical trial and get the cure is the funds.
The association works together with Rare Trait Hope Fund, a 501(c)(3) registered charity in the United States and Rare Trait Hope Society registered in Vancouver Canada to raise money to fund expenses associated with the preparation for and conduct of an upcoming gene therapy clinical trial. Together, we need to raise US$4 million and we hope to raise CHF500,000 of that here in Switzerland
Thanks to the combined efforts of parents of affected children in the USA, France, Canada, Australia, Spain, and the academic work of professors, researchers, geneticists, and other scientists, important advances have been made in gene therapy that suggests a very near cure for affected patients.
No research to develop a cure for AGU had been conducted anywhere in the world before 2012. Parents of two children with AGU located in the United States organized and funded private research at the University of North Carolina. The aim of the research was to develop a cure for AGU.
Based on the efforts of these two parents, many activities were completed including animal study, safety study, completion of natural history study in humans, and deposit of a pre-IND (initial new drug request) to the FDA (Food & Drug administration) in the USA. The organization of a clinical trial in humans is underway. Due to the extreme rarity of the disease, funding this trial is a real challenge for families of AGU patients.
Rare Trait Swiss wishes to combine its efforts with those of associations such as Rare Trait USA , Rare Trait Hope in Canada and “Vaincre l’AGU” in France which are working to facilitate the remaining research and development work necessary to treat and cure AGU. The funds raised will support the information of this very little known disease and the funding of the clinical trial. We will seek financial contributions for this including, but not limited to, individuals, nonprofits, government agencies, and businesses.
Aspartylglucosaminidase (AGA) enzyme normal function:
Its function is proteolytic, degrading glycoprotein via hydrolytic deglycosylation. Formally classed as a hydrolase (EC 126.96.36.199), it is a member of a family called the Ntn (N-terminal nucleophilic) hydrolases. These enzymes are characterized by coding as a large pre-protein and are post-translationally cleaved by autoproteolysis to create α- and β-subunits and a new N-terminal amino acid. The heterotetrameric AGA enzyme has two active sites, consisting of an essential conserved β-chain N-terminal threonine within an active site of deep conical profile. The enzyme is novel in that it requires both the α-amino and the α-carboxyl group of the substituted amino acid residue to be free. Additionally, the same Thr residue is involved both in genesis of the active enzyme, and in catalytic function of the active site.
There are a lot of steps involved getting a treatment to clinical trial. We are in the process of finalizing the location of the clinical trial and identifying and retaining a project manager with research experience to manage the Investigational New Drug process with the FDA and establish the treatment protocol. The money we are raising will be used to cover expenses associated with the preparation for and conduct of the clinical trial. These include travel, lodging and meeting fees, drug manufacturing, testing (safety, biodistribution and kinetics), clinical fees, hospital fees, clinical research organization costs (data processing) and related costs. It sounds like a lot, but we are actually SO CLOSE!!! We anticipate needing to raise US$2 million and we hope to raise CHF500,000 of that here in Switzerland