Featured: Genetic risk for Multiple Sclerosis originated in Pastoralist Steppe populations

William Barrie, et al. Department of Zoology, University of Cambridge

Summary: Using the largest ancient genome dataset from the Stone Age, along with new Medieval and post-Medieval genomes,  this large, international team shows that many of the genetic risk variants for MS rose to higher frequency among pastoralists located on the steppes of what is today Eastern Europe, Ukraine, and Russia, and were brought into Europe approximately 5,000 years ago. The authors assert that these MS-associated immunogenetic variants provided an evolutionary advantage, probably in response to pathogenic challenges coinciding with dietary and lifestyle environmental changes. This study highlights the critical importance of this period as a determinant of modern immune responses and its subsequent impact on the risk of developing MS in a changing environment. Population geneticist, Jed Carlson, calls this "a fascinating study and an important contribution to the population genetics literature".

Clinic Notes:

Metabolic costs of walking and arm reaching in persons with mild multiple sclerosis

Robert Courter et al, Department of Integrative Physiology, University of Colorado Boulder

Investigating what Dr. Mike Racke calls, "a novel concept for why MS patients have slower movements", the  authors measured energy expenditure and movement speed related to walking and reaching in PwMS vs. controls. Energy expenditure is significantly higher in PwMS during walking, but not in arm reaching activities. Nonetheless, movement is significantly slower in PwMS. The authors suggest that this may reflect diminished dopamine rewards related to grey matter atrophy.

Disability in Multiple Sclerosis is Associated with Vascular Factors: An Ultrasound study

Merlisa Kemp et al, Medical Imaging and Therapeutic Sciences, Cape Peninsula University of Technology

In this cross-sectional study of PwMS, subjects who a had decreased cerebral blood flow had increased levels of disability even after adjustment for age. These findings suggest a possible benefit in modification of diet and lifestyle among people with MS above and beyond the direct effects on cardiovascular health in pwMS, but the design limits our ability to draw firm conclusions.

Machine-learning-based prediction of disability progression in multiple sclerosis: an observational, international, multi-center study

Edward De Brouwer et al, Esat-Stadius, KU Leuven, Belgium

This study gathered data on disease progression in MS from 15,240 people with MS from 146 centers in 40 countries to develop an algorithm for the prediction of disease progression using machine learning. The authors have made the model freely available at https://gitlab.com/edebrouwer/ms_benchmark.

Cinta Lleixà et al, Department of Neurology, Institut d’Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona

The authors identify a antibodies to the flotillon-1/2 complex in 6 out of 252 PwMS and in none of the control subjects. The results suggests that the auto-antibodies may play a role in a small subset of PsMS.

Lab Notes

Circulating B Cells in Relapsing-Remitting Multiple Sclerosis Show Markedly Different Patterns of Regulatory Marker Expression Compared with Healthy Controls

Daniel W. Mielcarz et al, Departments of Microbiology/Immunology and the Dartmouth Cancer Center, Geisel School of Medicine at Dartmouth

"Taken together, these results indicate a potential for differential 29 regulation of B cells in RRMS patients that may provide an avenue for B cell 30 directed therapies for the disease."

Biochemical and metabolic maladaption defines pathological niches in progressive multiple sclerosis

Melissa Grant-Peters et al, Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford

"We employed high-resolution multiomic profiling to characterise the biochemical and metabolic adaptations underpinning MS pathology..."

Functional impairment of the Lateral Geniculate Nucleus in Multiple Sclerosis

Neda Sardaripour et al, Department of Biomedical Engineering, K. N. Toosi University of Technology (KNTU)

"In summary, we showed functional abnormalitiesin LGN structureandits M and P subdivisionsbased on functional MRI. "

MHC class I and MHC class II reporter mice enable analysis of immune oligodendroglia in mouse models of multiple sclerosis

Em P Harrington et al, Department of Neurology, Johns Hopkins University School of Medicine & The Ohio State University College of Medicine

"We generated MHC class I and II transgenic reporter mice to define their dynamics in response to inflammatory demyelination, providing a means to monitor MHC activation in diverse cell types in living mice and define their roles in aging, injury and disease."

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