CURRENT AND RECENT SMA RESEARCH PROJECT FUNDING

Most recent awards:

1. Rasch Analysis of Functional Scales used to Assess SMA

In September 2010 the Trust contributed €3,000 to SMA Europe’s support of a project being coordinated by the SMA Foundation in New York.

This project is part of an international effort to prepare the way for meaningful clinical trails. Gathering data is an important part of this process, but it is crucial that this data can be used and understood by all those involved in running trials. Investigators from at least seven groups have agreed to share de-identified data to facilitate evaluation of the comprehensiveness and sensitivity of the scales in SMA. Stefan Cano (Peninsula College, UK) and Anna Mayhew (Newcastle, UK) have agreed to perform the analysis.


A Rasch analysis of functional scale data collected from SMA patients will aid understanding of how the scales work in the SMA patient population. The overall goal of the Rasch Analysis Project is to identify whether there is a need to improve the current scales for use as outcome measures in clinical trials, and if so, how best to do this.



2.The SMA Trust has a history of supporting SMA research at the University of Oxford

Currently a grant of £139,000 is being made for a two year project which started in January 2010, supervised by Dr Kevin Talbot, entitled “Identification of the critical time point for SMN replacement therapy using a tetracycline repressible SMN transgenic mouse model.” The research is being carried out by Dr Angelika Biba.



Purpose of project
Current drug trials are mostly of agents which increase the level of SMN protein. However, the timing of SMN therapy has not been determined. This study will inform future clinical trials by exploring the effect of increasing SMN in mouse models at different time points. In particular it will identify if SMN reduction past the normal period of neuromuscular development still has an effect.


3. University of Edinburgh

At the Centre for Integrative Physiology & Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh:

Professor Thomas Gillingwater
Research Project: “Muscle pathology and biomarkers in SMA”
This two year project started on 1 June 2010: £62,000


Project outline
Professor Gillingwater’s team is using samples from both mice and SMA patients to examine molecular changes occurring in differently affected groups of muscles throughout the progression of the disease. These experiments will potentially identify new therapeutic targets to prevent or slow muscle wasting. They will also identify proteins which can be used to measure and compare disease progression in different SMA patients. This is critical for testing the effectiveness of new treatments for SMA in clinical trials.


UPDATE

Six Month Progress Report: “Muscle Pathology and Biomarkers in SMA” 1 November 2010

 
This project has two main aims:
1) to identify the role that muscle plays in the onset and progression of SMA
2) to identify muscle-specific biomarkers that can be used in animal and human clinical trials for SMA to accurately measure and compare disease progression within and between patients

The first attempts to use a state-of-the-art label-free proteomics approach to examine protein expression levels in muscle from SMA mice and littermate controls surpassed expectations, generating a large volume of high quality data. As a result, the experiments required to address the first aim are nearly complete. Muscle samples from SMA mice at pre-symptomatic stages have been examined and the data show that reduced levels of SMN protein have a direct effect on muscle, independent of the pathological events known to occur in lower motor neurones. This provides important evidence that muscle is an early pathological target in SMA.

These experiments have also identified key molecular pathways that are disrupted in SMA muscle, providing insights that will assist with the development of therapeutic strategies to target muscle in SMA patients.

This work was presented as a poster at the recent UK SMA Researchers Conference in Wales in October 2010.

4. The SMA Trust’s involvement with SMA Europe

Grant commitments totalling approximately €626,000 were made by SMA Europe for research projects in 2009 (contribution by the SMA Trust 45%)

Call for Research Projects 2009.
The seven institutions and researchers which attracted support were:
• Columbia University, New York, USA: Professor Umrao Monani
“Investigating the temporal requirements of the SMN protein in SMA”
• Molecular Genetics Institute of Montpellier, France: Professor Rémy Bordonne
“The S. pombe model organism: a tool to find suppressors of snRNP-mediated splicing defects”
• University of Sheffield: Dr Ke Ning and Professor Mimoun Azzouz
“PTEN modulation effects on motor neuron axonal growth and neuromuscular junction size in spinal muscular atrophy”
• University of Western Australia: Professor Steve Wilton
“Antisense oligomer induced restoration of SMN expression as a therapy for Spinal Muscular Atrophy”
• University of Bern, Switzerland: Dr Rachel Nlend Nlend
“Gene therapy for spinal muscular atrophy by a correction of SMN2 mRNA splicing”
• INSERM, Université de Nantes, France: Dr Beatrice Joussemet
“Evaluation of new AAV-mediated gene therapy strategies in a feline model of Spinal Muscular Atrophy”
• Emory University, Atlanta, USA: Dr Claudia Fallini
“Analysis of mRNA transport and local protein synthesis in axons of SMA motor neurons”

Grant commitments totalling approximately €780,000 made by SMA Europe for research projects in 2008 (contribution by the SMA Trust 42%)

Call for Research Projects 2008
The six research centres which attracted support were:
• University of Lisbon; Professor Margarida Gama Carvalho
“Characterization of post-transcriptional control mechanisms regulating SMN2 gene expression.”
• Università Cattolica, Rome: Professor Eugenio Mercuri
“Outcome measures in SMA types II and III”
• University of Milan: Professor Giacomo Pietro Comi
“Development of a stem cell approach for treating Spinal Muscular Atrophy”
• Institut de Myologie, Paris : Dr Martine Barkats
“Evaluation of AAV-mediated gene therapy in murine and feline SMA models”
• University of Missouri, USA: Dr Monir Shababi
“A Two-Pronged Approach to Develop a Treatment for Spinal Muscular Atrophy”
• Paratek Pharmaceuticals: Dr Paul Higgins
“Tetracycline Coumpounds as SMN2 splicing Modifiers for the Treatment of SMA”