Association of Insulin-like Growth Factor 1 Concentrations with Risk for and Prognosis of Amyotrophic Lateral Sclerosis - Results from the ALS Registry Swabia.

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Scientists in South-West of Germany, have investigated the associations of serum concentration of insulin-like growth factor 1 (IGF1) with prognosis of ALS in their region ALS registry in a case-control and cohort study, respectively.

Their study showed a clear association of low serum IGF-1 concentration with the prognosis of ALS, suggesting that higher IGF-1 concentration could increase survival.

There is growing evidence that a disturbed energy metabolism in ALS could play a pathogenic role. Data from Swabia's ALS registry showed a possible positive association of body mass index (BMI) with ALS decades before the clinical manifestation of ALS. In the ALS cases, there was a sharp kink in BMI trajectories shortly before onset of ALS, and greater weight loss was associated with a worse prognosis.

Insulin-like growth factor 1 (IGF-1) is a pluripotent growth factor with multiple functions in the peripheral and central nervous system. It supports neuronal survival and axon growth. IGF-1 led to increased survival of ALS patients in most but not all studies. It has also been the subject of several positive clinical trials, but it has undesired side effects. However results of a recent trial on IGF-1 in the treatment of spinal and bulbar muscular atrophy (SBMA), a rare motoneuron disease of the peripheral muscle with slow progression, did not improve muscle strength or function20.

The objective of this study was to analyze the associations of serum IGF-1 concentrations with the risk of ALS in a population-based case-control study. Furthermore, they investigated the association of IGF-1 serum concentration with prognosis of ALS in a cohort-design in ALS-cases only.

The ALS registry Swabia is a population-based clinical-epidemiological registry with the aim to collect data on all newly diag-nosed ALS cases in Swabia, a defined geographic region with approximately 8.4 million inhabitants in the South-West of Germany.

In this population-based case-control study in Southern Germany, serum IGF-1 concentrations were not associated with risk of ALS. In the cohort of ALS patients, however, they found evidence for an inverse association between high serum IGF-1 concentrations and overall survival. their results in the ALS cohort concerning prognosis are in line with observations of others.

Their observation that higher IGF-1 concentration is associated with longer survival is consistent with experimental research, showing that IGF-1 acts as a mitochondrial protector in the ALS cell and mouse model.

Multiple mechanisms elicited by IGF-1 might account for the observed increased survival in patients with higher circulating IGF-1. IGF-1 displays high neurotrophic properties, which could protect motor neurons and increase survival in ALS25. IGF-1 has also anabolic actions on skeletal muscle, especially upon denerva-tion26, which might be beneficial in ALS. Since IGF-1 is also related to energy metabolism and body weight, their current findings are consistent with former observations concerning BMI and adipokines as well as the findings on retinol binding protein (RBP)4 and the prognosis of ALS.

However, the observed protective effect of higher IGF-1 was observed upon adjustment of BMI, suggesting that it is not fully mediated by BMI as marker for fat mass. Thus, the longer survival of patients with higher IGF-1 levels could be related to direct biological actions of IGF-1, to an overactivation of a protective GH-IGF-1 pathway or to altered IGF-1 levels in patients with a favorable metabolic status.

So very high values IGF-1 are associated with a better prognosis of ALS suggesting that biological functions related to IGF-1 could be involved in ALS survival.

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