Metabolic therapies may have potential
There is potential for specific metabolic treatments that may prevent obesity in people with SPG 11.
People with SPG11 are found to have profound changes in body composition, with increased fat tissue and decreased lean tissue indices, and decreased muscle mass. Certain metabolic biomarkers in the blood were also altered and the volume of the hypothalamus in the brain was found to be reduced.
Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking.
Methods: In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI.
Results: Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients.
Conclusions: Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11.
SOURCE: Nutrients. 2022 Nov 13;14(22):4803. doi: 10.3390/nu14224803. PMID: 36432490
Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia
Martin Regensburger 1 2 3 , Laura Krumm 2 , Manuel Alexander Schmidt 4 , Andreas Schmid 5 , Imke Tabea Spatz 1 , Dominique Cornelius Marterstock 4 , Christoph Kopp 6 , Zacharias Kohl 1 , Arnd Doerfler 4 , Thomas Karrasch 5 , Beate Winner 2 3 , Jürgen Winkler 1 3
1. Division of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
2. Division of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
3. Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, 91054 Erlangen, Germany.
4. Institute of Neuroradiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
5. Department of Internal Medicine III, Gießen University Hospital, 35392 Giessen, Germany.
6. Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.