ATH434 studies target better brain function as was seen in the animal studies. The better function requires the nerves to get back their myelination. The high value of neurofilaments in the blood of MSA patients tells the speed of myelin degeneration of the nerves. At the moment we do not know how to visualize the possible remyelination of the brain after 434 treatment if and when the function improves as in the animal studies.

Multiple sclerosis is also a demyelination disease. In the report below we can see how remyelination is visualized in the MS patients. As you can see in the paper, iron has a big role in remyelination, MSA and MS are different, but remyelination could be very similar in both diseases.

Neurology

. 2024 Sep 24;103(6):e209604.

doi: 10.1212/WNL.0000000000209604. Epub 2024 Aug 30.

Quantifying Remyelination Using χ-Separation in White Matter and Cortical Multiple Sclerosis Lesions

Jannis Müller ¹, Po-Jui Lu ¹, Alessandro Cagol ¹, Esther Ruberte ¹, Hyeong-Geol Shin ¹, Mario Ocampo-Pineda ¹, Xinjie Chen ¹, Charidimos Tsagkas ¹, Muhamed Barakovic ¹, Riccardo Galbusera ¹, Matthias Weigel ¹, Sabine A Schaedelin ¹, Yi Wang ¹, Thanh D Nguyen ¹, Pascal Spincemaille ¹, Ludwig Kappos ¹, Jens Kuhle ¹, Jongho Lee ¹, Cristina Granziera ¹

Affiliations Expand

• PMID: 39213476

PMCID: PMC11362958 DOI: 10.1212/WNL.0000000000209604

Abstract

Background and objectives: Myelin and iron play essential roles in remyelination processes of multiple sclerosis (MS) lesions. χ-separation, a novel biophysical model applied to multiecho T2*-data and T2-data, estimates the contribution of myelin and iron to the obtained susceptibility signal. We used this method to investigate myelin and iron levels in lesion and nonlesion brain areas in patients with MS and healthy individuals.

Methods: This prospective MS cohort study included patients with MS fulfilling the McDonald Criteria 2017 and healthy individuals, aged 18 years or older, with no other neurologic comorbidities. Participants underwent MRI at baseline and after 2 years, including multiecho GRE-(T2*) and FAST-(T2) sequences. Using χ-separation, we generated myelin-sensitive and iron-sensitive susceptibility maps. White matter lesions (WMLs), cortical lesions (CLs), surrounding normal-appearing white matter (NAWM), and normal-appearing gray matter were segmented on fluid-attenuated inversion recovery and magnetization-prepared 2 rapid gradient echo images, respectively. Cross-sectional group comparisons used Wilcoxon rank-sum tests, longitudinal analyses applied Wilcoxon signed-rank tests. Associations with clinical outcomes (disease phenotype, age, sex, disease duration, disability measured by Expanded Disability Status Scale [EDSS], neurofilament light chain levels, and T2-lesion number and volume) were assessed using linear regression models.

Results: Of 168 patients with MS (median [interquartile range (IQR)] age 47.0 [21.7] years; 101 women; 6,898 WMLs, 775 CLs) and 103 healthy individuals (age 33.0 [10.5] years, 57 women), 108 and 62 were followed for a median of 2 years, respectively (IQR 0.1; 5,030 WMLs, 485 CLs). At baseline, WMLs had lower myelin (median 0.025 [IQR 0.015] parts per million [ppm]) and iron (0.017 [0.015] ppm) than the corresponding NAWM (myelin 0.030 [0.012]; iron 0.019 [0.011] ppm; both p < 0.001). After 2 years, both myelin (0.027 [0.014] ppm) and iron had increased (0.018 [0.015] ppm; both p < 0.001). Younger age (p < 0.001, b = -5.111 × 10^-5), lower disability (p = 0.04, b = -2.352 × 10^-5), and relapsing-remitting phenotype (RRMS, 0.003 [0.01] vs primary progressive 0.002 [IQR 0.01], p < 0.001; vs secondary progressive 0.0004 [IQR 0.01], p < 0.001) at baseline were associated with remyelination. Increment of myelin correlated with clinical improvement measured by EDSS (p = 0.015, b = -6.686 × 10^-4).

Discussion: χ-separation, a novel mathematical model applied to multiecho T2*-images and T2-images shows that young RRMS patients with low disability exhibit higher remyelination capacity, which correlated with clinical disability over a 2-year follow-up.