Objective: Quantify cortical perfusion at baseline and six months after a single infusion of allogeneic bone marrow-derived mesenchymal stem cells (allo-hMSC) in relation to demographic and clinical variables.

Background: Our phase I trial found allo-hMSC infusion to treat Parkinson’s disease (PD) to be safe [1], but relationships between imaging, demographic, molecular  and clinical measures remain to be explored.

Method: 20 patients with mild/moderate PD had 3T MRI including pulsed, continuous arterial spin labelling at baseline and 6 months after an infusion dose of 1,3, 6, or 10 x 10⁶ allo-hMSC/kg (5 patients per dose). Data were analyzed with ExploreASL v1.21 [2], producing for each participant at each time point mean cerebral blood flow (CBF) in cortical gray matter and spatial covariation, CoV, defined as the standard deviation of CBF divided by mean CBF within cortical gray matter. Mean CBF, CoV, age, duration of disease (DoD), MoCA, UPDRS-III, TNFa, BDNF, and CCL-2 at baseline and 6 months were entered into stepwise linear regressions with JASP v0.14.1.

Results: At baseline CBF showed a significant negative relationship between age and CBF (t=-2.459, p=0.024), while CoV regression found a three variable model to be significant (F_(3,16)=9.164, p<0.001) including positive relationships with CCL-2 (t=3.302, p=0.005) and DoD (t=3.303, p=0.004) but not age, and a negative relationship with MoCA (t=-2.502, p=0.024). At 6 month change in CBF found a positive relationship with age (t=2.478, p=0.023); there was no significant effect of age or any other independent variables in relation to 6 months CoV change despite marginally significant correlations between CoV change and changes in BDNF (r=-0.364, p=0.114) and TNFa (r=0.308, p=0.187).

Conclusion: We found that CBF was lower with increasing age at baseline, and six months later, higher CBF was found in older patients. However, CoV, a metric suggested to be even more robust than CBF, had no significant age-related changes[3]. At baseline, CoV increases along with CCL-2 and DOD and decreases with MoCA. The CoV baseline changes might be explained by the neuroinflammatory process of PD. CBF change could potentially be used as an efficacy marker for future trials. It will be essential to reassess both measurements in a larger trial to understand cortical perfusion change determinants.

References: 1. Schiess, M.C., Suescun, J., Doursout, M., Adams, C., Green, C., Saltarrelli, J.G., Savitz, S., Ellmore, T.M., (2021) Allogeneic bone marrow-derived mesenchymal stem cells safety in idiopathic Parkinson’s disease. Movement Disorders, Mar 2, 2021; (accepted). 2. Mutsaerts, H.J., Petr, J., Groot, P., Vandemaele, P., Ingala, S., Robertson, A.D., Václavů, L., Groote, I., Kuijf, H., Zelaya, F. and O’Daly, O., 2020. ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies. NeuroImage, 219, p.117031. 3. Mutsaerts, H.J., Petr, J., Václavů, L., Van Dalen, J.W., Robertson, A.D., Caan, M.W., Masellis, M., Nederveen, A.J., Richard, E. and MacIntosh, B.J., 2017. The spatial coefficient of variation in arterial spin labeling cerebral blood flow images. Journal of Cerebral Blood Flow & Metabolism, 37(9), pp.3184-3192.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/baseline-and-six-months-change-in-cortical-perfusion-in-a-mesenchymal-stem-cell-trial-for-parkinsons-disease/