The purpose of SMA Europe is to provide a framework to stimulate collaboration and accelerate translational research pathways in SMA and promote patient care.

SMA Europe is a non-profit organisation.

SMA Europe

The purpose of SMA Europe is to provide a framework to stimulate collaboration and accelerate translational research pathways in SMA and promote patient care.

SMA Europe is a non-profit organisation.

Latest News

28/09/2016

Roche initiates phase 2 clinical trials for RG7916 in Types 1, 2 & 3 SMA.

Roche initiates phase 2 clinical trials for RG7916. The company will be testing RG7916, an orally available drug that aims to correct the splicing of SMN2, the “backup gene”, in types 1, 2 & 3 SMA, at sites in the US, Canada, Australia and some European countries. There will be two trials. One will be a […]

26/09/2016

Biogen to file application for Nusinersen to EMA over coming weeks

Dear members of the SMA community, In response to your requests for information, we want to provide an update on the important progress made in moving the compound development program forward. Today we have achieved a crucial step in the pathway to approval of nusinersen. We have completed the submission of our New Drug Application […]

23/09/2016

A role for mitochondria in SMA

A team at Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago discovers a role for mitochondria in SMA. They identified functional and structural defects to the cells’ power houses, called mitochondria, which contribute to the motor neuron’s degeneration. These defects occur before the onset of SMA symptoms. Although the […]

Latest Projects

The ROCK-ERK signalling network in SMA – mediator of neurodegeneration and SMN independent treatment target

Dr. Niko Hensel Institute of Neuroanatomy, Hannover Medical School, Germany.

ROCK-ERK signalling pathway in SMA

Dr. Niko Hensel, Institute of Neuroanatomy at Hannover Medical School in Germany, has been granted an SMA Europe award to investigate the ROCK-ERK signalling network in SMA. Spinal Muscular Atrophy is a disease characterised by a loss of muscle control. This is caused by degeneration of specific cells in the spinal cord, the motor neurons. Cell death and survival is controlled by two proteins called ROCK and ERK. In SMA, they exhibit an enhanced activity.

Dr. Hensel will look at the effects of reducing  their activity back to normal levels in SMA model mice which have similar symptoms to human patients. Dr. Hensel will use two different approaches. First, he will use drugs which are known to inhibit ROCK and ERK and which have already been approved to treat other diseases. In addition, he will use antisense oligonucleotides enabling him to more specifically down regulate activities of the ROCK and ERK proteins.

The regulation of SMN function in SMA.

Dr. Olga Tapia,, University of Cantabria - Spain

Regulation of SMN functionThrough her two year fellowship, Dr. Olga Tapia will seek to understand the regulation of SMN function in the molecular pathophysiology of SMA.

Deletion or mutations of the SMN1 gene cause spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. The survival motor neuron (SMN) protein, encoded by the SMN1 gene, is essential for the biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and the molecular assembly of Cajal bodies (CBs). The CB is a nuclear compartment involved in the maturation and assembly of snRNPs implicated in the splicing of protein coding messenger RNAs (mRNA). That is to say that SMN plays an important role in the production of molecules important for the splicing of mRNA, the code for proteins.

While the role of SMN in the biogenesis of snRNPs has been studied extensively over the past 20 years, very little is known about the regulation of SMN functions by post-translational modifications (PTMs). In particular, the impact of PTMs of SMN on its interactions, protein stability and subcellular localisation. The identity of signaling pathways controlling SMN function in snRNP assembly remains a key question in the field and their elucidation has potential to open novel therapeutic avenues for the treatment of SMA.

What are the researchers aiming to do?

Dr. Tapia will seek to understand the regulation of SMN function by PTMs and their implication in the molecular pathophysiology of SMA.

How will the researchers do this?

Dr. Tapia will seek to see if the acetylation induced with HDAC inhibitors, nowadays used in SMA therapy, has any impact on SMN PTMs and functional regulation of the protein. In particular, they will determine whether the acetylation state of SMN impacts on its subcellular localization, interactions and stability, as well as on CB biogenesis, assembly of the splicing machinery and transcriptional activity. They will use cultured cells and mouse spinal cord motor neurons, the main target of reduced SMN function in human neuropathology.

About Dr. Tapia

Dr. Olga Tapia is a senior post-doctoral scientist at the laboratory of “Cell Biology of the Nucleus” at the University of Cantabria-IDIVAL in Santander (Spain).