A NOVEL THERAPY TRIAL FOR AGU DISEASE AT HUCH
We have recently started a novel investigator initiated therapy trial for AGU (aspartylglucosaminuria) with betaine in HUCH child neurology clinic. It is performed in collaboration with Prof. Ritva Tikkanen, University of Giessen. AGU is a progressive disease leading to mental retardation due to the accumulation of aspartylglucosamine in all tissues and also in the brain. It belongs to the Finnish disease heritage, and most of the patients are from Finland (about 160 alive patients). AGU disease is diagnosed by urine oligosaccharides at the average age of five, when global developmental delay is noticed. (Read more)
The drug is used for the first time in AGU, but is accepted for other purposes also in children. Prof. Tikkanen has shown that betaine activates AGA enzyme in patient fibroblasts in vitro in the case of homozygous AGUFin major mutation due to its small molecular chaperon characteristic. We have 21 AGU patients in the trial aged 7-15 years from the whole country (one patient lives in Sweden) who take the drug twice a day orally.
I follow up all the patients in the child neurology outpatient clinic at Peijas Hospital. We use urine aspartylglucosamine and serum AGA activity measurements as biomarkers for the effects of a drug in peripheral tissues. If these results are promising during the first year, the trial will continue for 3 more years to show possible effects in the central nervous system, which is studied by brain MRI and neuropsychological tests. If this mutation-specific treatment with betaine works in vivo like in vitro, we should diagnose these patients as early as possible to give the treatment in time and consider adding AGU disease to the neonatal screening panel in Finland.
A European medical company has donated the drug for the trial. The other major financial support comes from Jane and Aatos Erkko Foundation, but also Finnish AGU patient organization and HUCH participate in financing the trial.
In the US, also AGA gene therapy with AAV has been studied, and the results of intrathecal injection to the AGU mice have been promising. Probably a human phase 1 trial with a few adult patients will happen during next years.