FDA grants orphan drug designation to ALS gene therapy developed at UAB

The U.S. Food and Drug Administration (FDA) has granted the designation of gold drug to a new gene therapy for amyotrophic lateral sclerosis (ALS) developed at the Autonomous University of Barcelona and licensed to the North American company Klotho Neurosciences, Inc.

The drug uses a viral vector of the AAV (adeno-associated virus) type that expresses the secreted isoform of the Klotho protein (s-KL), with neuroregenerating, antioxidant and anti-inflammatory properties. In order to reach the neuromuscular junctions affected by ALS disease, the vector acts under the control of a DNA sequence that regulates the expression of the protein specifically in the muscle (a muscle-specific promoter), so that therapeutic activity is directed towards the neuromuscular junctions. This innovative approach has shown very promising results in the mouse model most commonly used for the preclinical study of ALS: it has delayed the onset of the disease, preserved neuromuscular function and extended survival.

The technological development has been led by UAB researchers, with the participation of CIBER, ICREA and Vall d'Hebron Research Institute, which are co-owners of the intellectual property licensed to Klotho Neurosciences (an emerging company based on knowledge generated at the UAB that will enter the Nasdaq in 2023) in relation to the Klotho protein. The technology has been developed by the research groups of Assumpció Bosch and Miguel Chillón, both from the UAB Department of Biochemistry and Molecular Biology and the UAB Institute of Neuroscience (INc-UAB). The research project has also involved the collaboration of the group of Professor Xavier Navarro, researcher at the Institute of Neurosciences and the Department of Cell Biology, Physiology and Immunology at the UAB, expert in neuroregeneration and motor neuron diseases.

‘The designation of gold standard drug for the therapy we have developed recognises the relevance of treatments aimed at the muscle and neuromuscular junction as a strategy for ALS,’ said Assumpció Bosch, principal investigator of the study. "For the moment we have been able to demonstrate its effectiveness in a reference animal model for this pathology. Now we are testing it in other ALS models to confirm that this therapeutic solution can be applied to the widest possible number of patients," said Sergi Verdés, postdoctoral researcher of the research team.

The FDA's designation as a gold standard drug recognises the potential of the treatment for a rare and severely disabling disease such as ALS, which affects around 65,000 people in Europe and for which there is no effective treatment. This recognition offers advantages such as seven years of drug exclusivity in the US market, tax reductions and tax incentives for preclinic trials.

Klotho Neurosciences will complete the production of the vector in order to start discussions with the FDA and the European Medicines Agency (EMA) in the near future, with the aim of moving towards the first clinical trials in patients.