OREANDA-NEWS. July 20, 2015. ENKAM Pharmaceuticals, the privately held biotechnology company based in Denmark, is pleased to announce that a partner in the Enkam-led NeuroFGL consortium has proven a novel marker for detecting in vivo neurogenesis using positron emission tomography (PET). The PET tracer [18F]-FLT was used to image the growth of neural stem cells in vivo using a pre-clinical stroke model.

The validation of [18F]-FLT in models of stroke is of significant interest because of its potential use in human clinical studies as a surrogate marker for stem cell activation, the formation of new neural cells and brain functionality. This means that it could potentially be very important in drug development for neurological diseases.

A team from the University of Cologne, leading this development as a part of the NeuroFGL consortium, used [18F]-FLT in a series of cell line and animal studies in which Enkam's novel compound FGLs, an allosteric fibroblast growth factor (FGF) receptor modulator, was compared with placebo.

[18F]-FLT is a bromodeoxyuridin analogue which becomes incorporated into the newly synthesized DNA of replicating cells. Thereby, it allows the visualisation of growing new neural stem cells.

The placebo-controlled studies by Prof. Dr. Michael Schroeter and his team at the University of Cologne, Germany, validated the use of [18F]-FLT by producing images that show the areas in the brain where neurogenesis was taking place and comparing these with histological examination to give an insight into the number and type of new cells and their differentiation. This analysis showed that FGLs enhances neurogenesis resulting in new neural cells.

The in vivo study in a rat model of middle cerebral artery occlusion, as the model of brain damage, showed that FGLs induced proliferation of neural stem cells in the subventricular zone and drives these to differentiate into oligodendrocyte precursors and neuroblasts as validated by supplementary cell culture experiments.

The [18F]-FLT PET tracer is being prepared for clinical testing in man and an application has been submitted to the German authorities. It will be a very important step forward for patients with neurodegenerative diseases as new drugs with potential neuro-regenerative effects will be able to be tested faster and more accurately.

The marker work was carried out as part of the NeuroFGL's studies of FGLs, funded by a €6.0 million grant from the European Union awarded four years ago. The grant has funded a Phase I clinical study of FGLs in Alzheimer's disease along with a number of marker technologies including an EEG-based bioactivity marker. The results from the Phase I clinical study are expected shortly.

Prof. Dr. Michael Schroeter, Principal Investigator of the Experimental Neuroimmunology Laboratory, University of Cologne, commented: "The application of [18F]-FLT PET has given us fascinating insights into the biology  of endogenous neural stem cells in CNS disease. Our vision is to use this technique to gain an insight into the reparative capacity of stimulating neural stem cells in neurodegenerative and cerebrovascular CNS disease."

Morten Albrechtsen, CEO of Enkam, commented: "The University of Cologne's work in validating the use of the PET tracer [18F]-FLT in a stroke model is potentially very important for drug development in neurological diseases. The stroke model results show that [18F]-FLT has potential utility as a marker for neurogenesis. This validation work has been carried out using Enkam's novel compound FGLs, which represents an exciting new approach to the potential treatment of neurodegenerative diseases. We look forward to working with the University of Cologne in using [18F]-FLT in a clinical study of FGLs."