case_images: PMC10569690_01
case_images: (A) Protocol approval timeline; (B) Cell culturing images for 26 infusions. Passage 4 culture images for all 26 infusions. Images were taken with a Leica inverted microscope at 50x magnification. Color variation is due to flask wall thickness, angle and light. *The product released for infusion #12 was lower than the minimum dose requirement of 200 (+-20%) million live cells. Low cell count was because of compromised cell growth due to growth medium issue.
case_images: fneur-14-1257080-g0001.jpg
case_images: PMC10569690_01_fneur-14-1257080-g0001.jpg
case_images: F1
case_images: After completing 20 infusion treatments, FDA approved 6 more infusions to the patient's protocol in January 2021, which continued at the same dose, but the interval changed from every 4 weeks to every 8 weeks (Figure 1A). For infusions, passage #2 cells were thawed, recovered in passage #3, and cultured to passage #4 (Figure 1B). A total of 26 infusions (manufactured from the cell bank created for the patient and freshly harvested from passage #4; Figure 1B), each with 200 million +-20% MSCs mixed in 20 mL of 0.9% sterile sodium chloride were administered intravenously over a period of ~2.5 year: 20 monthly infusions and remaining 6 infusions administered bimonthly.
case_images: UPDRS scores (A) Activities of Daily Living (part II): Improvements were seen in all measured parameters with significant improvements observed in "turning in bed and adjusting bed clothes" as well as "tremor" (left), with overall improvement in the total score (right); (B) Motor Examination (part III): Major improvements were noted in "rigidity" after only eight infusions of HB-adMSC therapy. Other motor symptoms that showed improvements included "facial expression," "tremors at rest," "hand movements," "leg agility," "gait," and "body bradykinesia and hypokinesia" (left), with substantial improvements in the total score (right); (C) Complications of Therapy (part IV): Significant improvements were observed in patient's "painful dyskinesia" (left) with an overall improvement observed in the total score (right).
case_images: fneur-14-1257080-g0002.jpg
case_images: PMC10569690_01_fneur-14-1257080-g0002.jpg
case_images: F2
case_images: Therapy (UPDRS part IV). The patient showed significant improvements in each of these areas:post-therapy, the patient demonstrated remarkable improvements in UPDRS part II, for each of the activities of daily living, compared to baseline (Figure 2A, left). Also, the total score for UPDRS part II showed significant improvements (score improved from 18 to 4) (Figure 2A, right). Similarly, several improvements were seen in the areas of motor examination UPDRS part III scores, with the most notable changes observed in patient's rigidity (Figure 2B, left). There was an overall improvement in her motor symptoms that included, tremors at rest, hand movements, leg agility, gait, as well as body Bradykinesia and Hypokinesia (the total UPDRS part III score improved from 14 to 2) (Figure 2B). Additionally, following HB-adMSC therapy, the patient's disabling dyskinesias were no longer severe; the total UPDRS IV score improved from 7 to 0 (Figure 2C).
case_images: FDG-PET scans. Brain metabolism is represented via a color spectrum with SUVR values ranging from low to high, consistent with colors ranging from blue/green/yellow (low SUVR) to orange/red (moderate SUVR) and bright red (high SUVR). (A) PDRP regions of characteristically low metabolism (parieto-occipital cortices): (left) cross-hairs focus on a region with relatively low metabolism at BL (SUVR = 1.08) that is increased at FU1 (SUVR = 1.15) and exhibits a subsequent decline at FU2 (SUVR = 1.04); (right) cross-hairs focus on the another portion of the parieto-occipital cortex with relatively lower metabolism at BL (SUVR = 1.18) that is increased at FU1 (SUVR = 1.26) and subsequently declines at FU2 (SUVR = 1.15); (B) PDRP regions of characteristically high metabolism images (thalamus, cerebellar cortices): (left) cross-hairs are centered on the left thalamus wherein relatively higher metabolism at BL (SUVR = 1.33) was slightly reduced at FU1 (SUVR = 1.29) and subsequently increased at FU2 (SUVR = 1.41); (middle) cross-hairs center on the cerebellar vermis with minimal change in SUVR values from BL (SUVR = 1.27) to FU1 (SUVR = 1.29) and subsequent increase to FU2 (SUVR = 1.47); (right) left cerebellar hemispheres show a reduction in SUVR values from BL (SUVR = 1.24) to FU1 (SUVR = 1.13) and a subsequent increase to FU2 (SUVR = 1.22). BL, baseline; FU1, follow-up 1; FU2, follow-up 2.
case_images: fneur-14-1257080-g0003.jpg
case_images: PMC10569690_01_fneur-14-1257080-g0003.jpg
case_images: F3
case_images: In the parieto-occipital cortex, relatively low metabolism was seen at the baseline (SUVR = 1.08), that was increased at FU1 (SUVR = 1.15) with a subsequent decline at FU2 (SUVR = 1.04) Figure 3A (left). The cross-hairs in Figure 3A (right), centered on a portion of the parieto-occipital cortex, showed relatively lower metabolism at baseline (SUVR = 1.18) that got increased at FU1 (SUVR = 1.26) with a subsequent decline at FU2 (SUVR = 1.15). Similarly, cross-hairs (centered on an aspect of the left cerebellar hemispheres) in Figure 3B (right) where a reduction in SUVR values from baseline (SUVR = 1.24) to FU1 (SUVR = 1.13) and subsequent increase at FU2 (SUVR = 1.22) was noted. Similar changes were observed in various locations throughout the left cerebellar hemisphere and in the right cerebellar hemisphere.