US 12,448,651 B2
Markers of disease prognosis in multiple sclerosis
Adi Vaknin-Dembinsky, Jerusalem (IL); and Iris Lavon Ben Moshe, Kfar Saba (IL)
Assigned to HADASIT MEDICAL RESEARCH SERVICES AND DEVELOPMENT LTD., Jerusalem (IL)
Appl. No. 17/413,480
Filed by HADASIT MEDICAL RESEARCH SERVICES AND DEVELOPMENT LTD., Jerusalem (IL)
PCT Filed Dec. 11, 2019, PCT No. PCT/IL2019/051353
§ 371(c)(1), (2) Date Jun. 11, 2021,
PCT Pub. No. WO2020/121305, PCT Pub. Date Jun. 18, 2020.
Claims priority of provisional application 62/778,325, filed on Dec. 12, 2018.
Prior Publication US 2022/0049309 A1, Feb. 17, 2022
Int. Cl. C12Q 1/6883 (2018.01)
CPC C12Q 1/6883 (2013.01) [C12Q 2600/118 (2013.01); C12Q 2600/158 (2013.01)] 10 Claims
 
1. A method for evaluating, at a first time point, the projected severity of multiple sclerosis (MS) at a second, subsequent time point at least ten years after the first time point, comprising:
a) obtaining a peripheral blood mononuclear cells (PBMC)-containing sample from a subject afflicted with MS at the first time point,
b) determining the RNA expression level of TIM-3 in the sample,
c) comparing the RNA expression levels determined in b) to the respective levels corresponding to a non-malignant negative control, and
d) determining the projected severity of MS at the second time point,
wherein a statistically significant reduction in the RNA expression level of TIM-3 in said sample compared to the respective control level is indicative of increased disease severity associated with a predicted malignant MS outcome in said subject at the said second time point compared to said first time point,
wherein lack of a statistically significant reduction in said RNA expression level of TIM-3 in said sample compared to the respective control level is indicative of a predicted benign MS outcome in said subject at said second time point compared to said first time point,
wherein said method further comprises the step of administering to said subject, based on the projected severity at said second time point, a suitable treatment selected from the group consisting of:
natalizumab, alemtuzumab, ocrelizumab, and/or cladribine if the predicted MS outcome is malignant; or
glatiramer acetate, interferon beta-1A, peginterferon beta-1A, interferon beta-1b, teriflunomide, and/or dimethyl fumarate if the predicted MS outcome is benign.