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

  1. Novel protective gene for SMA opens new therapeutic options

    The research group of Prof. Dr. Brunhilde Wirth, Head of the Institute of Human Genetics at the University Hospital Cologne and Chair of our Scientific Advisory Board, succeeded to identify calcineurin-like EF-hand Protein 1 (CHP1) reduction as a novel protective modifier for SMA. The results of this study have been published in Brain, an international highly renowned journal.

    Novel protective gene for SMA opens new therapeutic options

    Eva Janzen & Professor Wirth


    A major disease hallmark is the progressive loss of motor neurons, eventually leading to muscle atrophy and weakness. An early characteristic of SMA is the reduced size and maturation of the junction which connects the motor neuron to the muscle fibre. This junction, or neuromuscular junction (NMJ), is essential for the transmission of signals from the motor neuron to the muscle.

    The transmission of signals from the motor neuron to the muscle involves a mechanism called endocytosis, which recycles and transport molecules (signals) by engulfing them. This recycling is especially important in neurons, because these cells have to rapidly release signals to communicate with each other and with muscles. Without this specialised recycling, the signals are not recycled fast enough to keep up with nerve and muscle cell activity.

    In previous studies, Professor Wirth and her research group showed that plastin 3 (PLS3) was a protective genetic modifier in people who remained unaffected by SMA, despite carrying the genetic predisposition. Indeed, over-expression of PLS3 protects against SMA by restoring impaired endocytosis and  thereby signalling and NMJ maintenance in SMA.

    What were the researchers trying to find out?

    The exact mechanism through which PLS3 restores impaired endocytosis is largely unknown. Eva Janzen together with Natalia Mendoza-Ferreira and Seyyedmohsen Hosseinibarkooie, all from the Wirth lab, proceeded to look into this.

    What did they discover?

    The team proceeded to look for partners of PLS3. They identified a previously unknown molecule, called CHP1, which suppresses endocytosis through blocking another molecule called calcineurin. They then showed that reducing CHP1 restored calcineurin activity and this had beneficial effects in various SMA models by restoring impaired endocytosis. Moreover the team showed for the first time that calcineurin activity is diminished in SMA cells and thereby most likely contributes to the reduced endocytosis in SMA.

    Furthermore, they looked at the effects of combining CHP1 reduction with Spinraza™ and found that the survival of SMA mice was prolonged by 1.6-fold and the main disease hallmarks of SMA improved.


    Taken together, the scientists showed that CHP1 reduction is a novel protective mechanism for SMA which enhances SMN-increasing therapies.

    What does this mean for people living with SMA?

    Although Spinraza™ was recently approved by the FDA and EMA for the treatment of SMA, this SMN-increasing therapy seems insufficient to fully rescue severely-affected type I SMA patients. Therefore, combining an SMN-independent method such as CHP1 reduction, to an SMN-dependent therapy, is a highly promising therapeutic approach.

    Original publications