Friday, October 19, 2018

Trial Shows Positive Initial Results for IGF-1

This is a follow-up article written by Lucy Piper on the IGF-1 trials that is written more for the layperson. It was published in Medwire News. Click on the link below to read the article at Medwire.


Positive initial results for IGF-1 pathway as treatment target in spinal and bulbar muscular atrophy

medwireNews: The insulin-like growth factor-1 (IGF-1) pathway may be a suitable treatment target for patients with spinal and bulbar muscular atrophy, suggest preliminary findings.

“By targeting the IGF-1 pathway in spinal and bulbar muscular atrophy, we aimed to replenish the reduced IGF-1 concentrations found in this disease, to stimulate downstream Akt activity to reduce the toxicity of the mutant androgen receptors, and to increase anabolic activity to prevent muscle loss”, the researchers explain.

They examined the tolerability and preliminary efficacy of the IGF-1 mimetic BVS857 in 27 patients, of whom 18 who were randomly assigned to receive the drug while nine were assigned to placebo.

The patients, aged at least 18 years, were ambulatory, had symptomatic weakness and had serum IGF-1 levels of 170 ng/mL or below.

The patients given BVS857 0.06 mg/kg intravenously once a week for 12 weeks showed a significant improvement from baseline in thigh muscle volume – a marker of muscle wasting and denervation – on magnetic resonance imaging scans, compared with placebo, with a geometric mean ratio of 1.04 in favour of the treatment.

Specifically, thigh muscle volume remained stable in the patients taking BVS857, whereas it declined in the placebo group over the course of treatment.

Improvements in the Adult Myopathy Assessment Tool score were seen in both groups, at 7.0% in the placebo group and 4.9% in those taking BVS857, but there was no significant difference between the two. There was also no change in lean body mass in either group.

There was a similar positive change in EQ-5D score for the two groups and a significant improvement with BVS857 over placebo in SF-36 Mental Component Score.

The researchers, led by Christopher Grunseich (National Institutes of Health, Bethesda, Maryland, USA), note in The Lancet Neurology that there was no treatment effect on muscle function, which may be “a consequence of the small effect on muscle volume.” And there was no increase in Akt signalling in monocytes or muscle biopsy samples possibly as a consequence of “the short duration of the increase in total IGF-1 equivalency”, they propose.

In a related commentary, Atsushi Hashizume and Masahisa Katsuno, both from Nagoya University Graduate School of Medicine in Japan, say that the discrepancy between a positive drug effect on thigh muscle volume and clinical outcomes “suggests a need for identification of novel biomarkers that reflect both biological and clinical effects of IGF-1 mimetics and related drugs.”

They add that “extension of the half-life of IGF-1 is key to improving the biological effects of this therapy in patients with spinal and bulbar muscular atrophy.”

BVS857 was otherwise generally well tolerated, with no cases of hypoglycaemia, Bell’s palsy or serious adverse events. However, immunogenicity was detected in 72% of patients taking BVS857, which “limits its use as a therapeutic drug”, note Grunseich and team.

They conclude that the findings are “encouraging” and call for further trials with sufficient power and longer duration to better assess the effects of IGF-1 targeting on muscle strength and function.

“Activation of the IGF-1 pathway by other means, perhaps in combination with anti-androgen drug[s], might be worth pursuing in future trials,” they suggest.

By Lucy Piper

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

Image:  https://www.alpco.com/role-igf-1-growth-hormoneigf-axis

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