**Acknowledgements**

authors concluded that IGF-1 does not provide benefits for ALS patients. No preclinical studies have demonstrated any beneficial effects of subcutaneously administered IGF-1 either. Positive outcomes were only observed after intrathecal injections or when the trophic factor was delivered with a viral vector, indicating that the method of administration might be crucial for successful treatment. Another study conducted on nine ALS patients intrathecally injected with IGF-1 every 2 weeks for 40 weeks reported that their method of administration caused

GLP-1 is an endogenous peptide responsible for controlling plasma glucose levels by stimu‐ lating insulin synthesis and its secretion from pancreatic β cells [76]. So far, little is known regarding the role of GLP-1 in the physiology of neural tissue. However, GLP-1 receptors have been observed on the neurons of various brain regions, including the hippocampus, cerebel‐ lum, and cerebral cortex [77], indicating that it is involved in proper neuronal function. GLP-1 protects neural cells from excitotoxicity [78] and participates in learning and memory processes [79]. All of these features make GLP-1 a potentially useful factor to investigate for ALS therapy. An in vitro study using motor neurons derived from Sod-1 (G93A) transgenic mice that were exposed to kainite (excitotoxic stimulus) reported that a synthetic analogue of GLP-1 exhibited neuroprotective effects [80]. The neuroprotective potential of GLP-1 has also been tested in a mouse model of ALS. Human MSCs were transfected with a plasmid vector encoding *GLP-1*, encapsulated and subsequently injected into the cerebral ventricle [81]. This method of treatment significantly prolonged the lifespans of treated animals (by 13 days), delayed symptom onsets, decreased weight loss, and caused improvements in motor performance tests. These data suggest that GLP-1 may become a new target for ALS therapeutic research. However, further in vivo studies optimizing administration route and delivery methods

should be conducted in animal models before effective use in any clinical trial.

As long as the exact cause of ALS remains elusive, it will be hard to propose any fully effective and accurately targeted form of therapy. Therefore, clinical trials should consider the broadest spectrum of neuroprotection possible. However, the methods employed have not always been standardized based on the results of preclinical research in animal models, resulting in ambiguous results in different studies performed in ALS patients. Since trophic factors have the ability to support survival and strengthen the functions of neural cells, further, more extensive studies are required to precisely investigate the real role of humoral activity in the natural history of ALS. To date, the most promising effects appear to be those obtained in studies employing VEGF and GDNF; however, clinical trials conducted on large numbers of

modest but significant beneficial effects [75].

**7. Glucagon-like peptide 1**

220 Update on Amyotrophic Lateral Sclerosis

**8. Conclusions**

patients remain lacking.

This is supported by the National Centre for Research and Development Grant STRAT‐ EGMED1/234261/2NCBR/2014.
