Study led by senior lecturer at the University of Hertfordshire reveals new insights into the pathophysiology of Spinal Muscular Atrophy
University of Hertfordshire
Study led by senior lecturer at the University of Hertfordshire reveals new insights into the pathophysiology of Spinal Muscular Atrophy.
- The research is part of Dr Maria Dimitriadi’s wider work on motor neuron diseases
- Findings reveal for the first time that the important process of endocytosis is defective in Spinal Muscular Atrophy (SMA)
- Dr Dimtriadi is setting up a new research facility at the University of Hertfordshire to continue exploration in this area
Dr. Maria Dimitriadi, Senior Lecturer in Molecular Genetics at the University of Hertfordshire, and her colleagues at Brown University and Albert Einstein College of Medicine in the US, are the first to pin point the cellular mechanism of endocytosis as being defective in Spinal Muscular Atrophy (SMA) — providing an exciting new lead for further investigations.
SMA, a devastating motor neuron disorder caused by depletion of the Survival Motor Neuron (SMN) protein, continues to be the most common cause of infant death. The connection between SMA and SMN has been known for years, but what remains a vital question is why diminished SMN levels specifically cause spinal neurons to die — leading to the weakening and wasting of patients’ muscles.
This new research paper published in the Proceedings of the National Academy of Sciences, for which Dr Dimitriadi was the lead author, identified endocytic defects in motor neurons and in non-neuronal tissues by using experiments in the nematode (roundworm) Caenorhabditis elegans and in human cells.
In addition to the lead finding, an unexpected twist of this study was the preliminary result that the SMA genetic trait might protect individuals from infectious diseases. From an evolutionary perspective, this could explain the increased number of SMA carriers in the general population. The idea of a genetic trait that causes a devastating neuromuscular disease but can also reduce one’s incidence of infection is very intriguing and remains to be further elucidated.
“What makes this study exciting is that it reveals for the first time that ‘endocytosis’ (a process by which cells transport and recycle molecules by engulfing them) is defective in the Caenorhabditis elegans worm model of SMA”, said Dr Dimitriadi. “As a next step, we are interested in identifying the mechanistic evidence behind the role of SMN depletion in neuron-specific endocytosis”
The findings and achievements of Dr. Dimitriadi’s work provide a huge opportunity and new direction for future research into this area. Dr Dimitriadi is currently setting up a new C. elegans research facility at the University of Hertfordshire, where further explorations with Caenorhabditis elegans can take place.
C. elegans have not only been useful with her research into SMA but are also proving to be hugely helpful in studying human health and disease, particularly in the fields of toxicology, neurobiology, developmental biology and genetics.
