The paper below tells how to measure iron overload and they use MRI measure of the liver. But my main point is that there are some 12% of the general population who have hyperferritinemia. That is the population who one day could need ATH434 (??), not only the few, perhaps 50.000 multiple system atrophy cases. Most of these "12% people" are metabolic syndrome cases and then the other big group are hemochromatosis cases. But first, we need to get a good safety evidence and efficacy report in the ph 2 studies. After that, there are a huge number of indications as I have posted, not only brain diseases (still very important) but many other degenerative diseases.

Original article

Hyperferritinemia and liver iron content determined with MRI: a new role for the liver iron index

Author links open overlay panelWenke Moris ^{1 2 3}, Jef Verbeek ⁴, Frans C. Bakers ⁵, Eva Rombout-Sestrienkova ^{2 6}, Ad A.M. Masclee ^{2 3}, Ger H. Koek ^{2 3}, Cees Th.B.M. van Deursen ^{1 2}

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https://doi.org/10.1016/j.clinre.2023.102224Get rights and content

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Abstract

Background

: Hyperferritinemia is found in around 12 % of the general population. Analyzing the cause can be difficult. In case of doubt about the presence of major iron overload most guidelines advice to perform a MRI as a reliable non-invasive marker to measure liver iron concentration (LIC). In general, a LIC of ≥ 36 µmol/g is considered the be elevated however in hyperferritinemia associated with, for example, obesity or alcohol (over)consumption the LIC can be ≥ 36 µmol/g in abscence of major iron overload. So, unfortunately a clear cut-off value to differentiate iron overload from normal iron content is lacking. Previously the liver iron index (LII) (LIC measured in liver biopsy (LIC-b)/age (years)), was introduced to differentiate between patients with major (LII ≥ 2) and minor or no iron overload (LII < 2). Based on the good correlation between the LIC-b and LIC determined with MRI (LIC-MRI), our goal was to investigate whether a LII_MRI ≥ 2 is a good indicator of major iron overload, reflected by a significantly higher amount of iron needed to be mobilized to reach iron depletion.

Methods

: We compared the amount of mobilized iron to reach depletion and inflammation-related characteristics in two groups: LII-MRI ≥ 2 versus LII-MRI < 2 in 92 hyperferritinemia patients who underwent HFE genotyping and MRI-LIC determination.

Results

: Significantly more iron needed to be mobilized to reach iron depletion in the LII ≥ 2 group (mean 4741, SD ±4135 mg) versus the LII-MRI < 2 group (mean 1340, SD ±533 mg), P < 0.001. Furthermore, hyperferritinemia in LII-MRI < 2 patients was more often related to components of the metabolic syndrome while hyperferritinemia in LII-MRI ≥ 2 patients was more often related to HFE mutations.

Conclusion

: The LII-MRI with a cut-off value of 2 is an effective method to differentiate major from minor iron overload in patients with hyperferritinemia.