Cardiovascular and organ pathology in spinal muscular atrophy

About the project

Spinal muscular atrophy is a fatal, childhood form of motor neurone disease, where death of the motor neurons, if untreated, results in paralysis followed by respiratory failure and premature death. SMA is now treatable, and patient survival and health are improving, but evidence suggest that we are not treating the whole disease.

It is now clear that the cell-ubiquitous depletion of the SMN protein, which is the cause of spinal muscular atrophy, results in a wide range of tissue pathologies beyond the motor neuron. Our work has revealed the extent of these systemic defects and is beginning to appreciate how they impact upon the disease. We are particularly interested in the microvascular system, and have reported extensive, cell-intrinsic defects in endothelial cells and in blood vessels in animal models and patients. Our work is focussed on understanding how SMN-depletion leads to blood vessel pathology, which affects not only tissue oxygenation, but also essential barriers such as the blood brain and blood spinal cord barriers.  Specifically, we want to know if these pathologies exacerbate SMA pathology, and if so whether they can be targeted therapeutically.


SMA Europe, Anatomical Society, Grampian Endowments, University of Aberdeen Development Trust


Zhou H, Hong Y, Scoto M, Thomson A, Pead E, MacGillivray T, Hernandez-Gerez E, Catapano F, Meng J, Zhang Q, Hunter G, Shorrock HK, Ng TK, Hamida A, Sanson M, Baranello G, Howell K, Gillingwater TH, Brogan P, Thompson DA, Parson SH, Muntoni F
Microvasculopathy in spinal muscular atrophy is driven by a reversible autonomous endothelial cell defect.
J Clin Invest. 2022 Nov 1;132(21):e153430
Gillingwater TH, McWilliam C, Horrocks I, McWilliam K, Hamilton M, Fletcher E, Williams N, Smith S, Parson SH.
A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland
Scott Med J. 2022 Feb;67(1):46-47
Deguise MO, Pileggi C, De Repentigny Y, Beauvais A, Tierney A, Chehade L, Michaud J, Llavero-Hurtado M, Lamont D, Atrih A, Wishart TM, Gillingwater TH, Schneider BL, Harper ME, Parson SH, Kothary R.
SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease.
Cell Mol Gastroenterol Hepatol. 2021;12(1):354-377.e3
Watson KS, Boukhloufi I, Bowerman M, Parson SH
The Relationship between Body Composition, Fatty Acid Metabolism and Diet in Spinal Muscular Atrophy
Brain Sci. 2021 Jan 20;11(2):131
Hernandez-Gerez E, Dall'Angelo S, Collinson JM, Fleming IN, Parson SH
Widespread tissue hypoxia dysregulates cell and metabolic pathways in SMA.
Ann Clin Transl Neurol. 2020 Sep;7(9):1580-1593
Allardyce H, Kuhn D, Hernandez-Gerez E, Hensel N, Huang YT, Faller K, Gillingwater TH, Quondamatteo F, Claus P, Parson SH
Renal pathology in a mouse model of severe Spinal Muscular Atrophy is associated with downregulation of Glial Cell-Line Derived Neurotrophic Factor (GDNF).
Hum Mol Genet. 2020 Aug 11;29(14):2365-2378
Hernandez-Gerez E, Fleming IN, Parson SH
A role for spinal cord hypoxia in neurodegeneration.
Cell Death Dis. 2019 Nov 13;10(11):861
Deguise MO, Baranello G, Mastella C, Beauvais A, Michaud J, Leone A, De Amicis R, Battezzati A, Dunham C, Selby K, Warman Chardon J, McMillan HJ, Huang YT, Courtney NL, Mole AJ, Kubinski S, Claus P
Murray LM, Bowerman M, Gillingwater TH, Bertoli S, Parson SH, Kothary R
Abnormal fatty acid metabolism is a core component of spinal muscular atrophy.
Ann Clin Transl Neurol. 2019 Aug;6(8):1519-1532
Šoltić D, Shorrock HK, Allardyce H, Wilson EL, Holt I, Synowsky SA, Shirran SL, Parson SH, Gillingwater TH, Fuller HR
Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy
Hum Mol Genet. 2019 Nov 1;28(21):3515-3527

Primary location


Principal Investigator

Other people involved

Hazel Allardyce, Kaja Kostenevec and Martin Collinson in Aberdeen

Prof Francesco Muntoni and Dr Haiyan Zhou at University College London

Prof Tom Gilllingwater and Prof Tom Wishart at University of Edinburgh