You are viewing a javascript disabled version of the site. Please enable Javascript for this site to function properly.
Go to headerGo to navigationGo to searchGo to contentsGo to footer
In content section. Select this link to jump to navigation

Human Growth Hormone Increases SMN Expression and Survival in Severe Spinal Muscular Atrophy Mouse Model

Article type: Research Article

Authors: MacKenzie, Duncan | Shamim, Fahad | Mongeon, Kevin; | Trivedi, Ankur | MacKenzie, Alex; | Farooq, Faraz

Affiliations: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada | University of Ottawa, Ottawa, Canada

Note: [] Correspondence to: Alex MacKenzie, MD, PhD., and Faraz Farooq, PhD., Children's Hospital of Eastern Ontario Research Institute, Apoptosis Research Centre, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada. Tel.: +1 613 737 2772; Fax: +1 613 738 4833; E-mails: [email protected], [email protected]

Note: [] Correspondence to: Alex MacKenzie, MD, PhD., and Faraz Farooq, PhD., Children's Hospital of Eastern Ontario Research Institute, Apoptosis Research Centre, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada. Tel.: +1 613 737 2772; Fax: +1 613 738 4833; E-mails: [email protected], [email protected]

Keywords: Spinal muscular atrophy, human growth hormone, SMN protein, STAT5 pathway, SMA mouse model, therapeutics

DOI: 10.3233/JND-140000

Journal: Journal of Neuromuscular Diseases, vol. 1, no. 1, pp. 65-74, 2014

Published: 2014
Get PDF open access
Supplementary Materials:

Supplementary Figures 1 and 2.

Supplementary Video.

Abstract

Background: Autosomal recessive spinal muscle atrophy (SMA) is characterized by the loss of α motor neurons resulting in progressive muscle loss and respiratory failure. SMA is one of the most common inherited causes of infant death with a carrier frequency of 1 in 50 and a calculated prevalence of about 1 in 11,000 live births in the US. The low amount of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene causes SMA. Objective: A potential treatment strategy for SMA is to upregulate levels of SMN protein originating from the paralog SMN2 gene compensating in part for the absence of the SMN1 gene. Our group has previously shown that activation of the STAT5 pathway by lactation hormone prolactin (PRL) increased SMN levels, improved motor function and enhanced survival in a severe SMA mouse model. Given that human growth hormone (HGH) is also known to activate the STAT5 signalling pathway and is already used extensively in clinical settings, we thus elected to assess its impact on SMN levels. Methods and Results: Administration of HGH in NT2 cells activated STAT5 pathway which resulted into significant induction in SMN protein levels. Furthermore, systemic administration of HGH to transgenic SMA mice induced SMN protein levels in the brain and spinal cord samples. Critically, HGH treatment improved disease phenotype and increased survival in two severe SMA mouse models. Conclusions: Our results confirm earlier work suggesting STAT5 pathway activators as potential therapeutic compounds for the treatment of SMA and identify HGH as one such promising agent.

Show less