Adipose-derived, autologous mesenchymal stem cell therapy for patients with post-COVID-19 syndrome: an intermediate-size expanded access program.

BACKGROUND: Evolving mutations of the novel coronavirus continue to fuel up the pandemic. The virus affects the human respiratory system along with other body systems, causing several sequelae in the survivors of the disease, presented as post-COVID-19 syndrome or long-COVID-19. This protocol utilized Hope Biosciences' autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to evaluate safety and efficacy of HB-adMSC therapy to improve signs and symptoms associated with post-COVID-19 syndrome. METHODS: Ten eligible subjects with post-COVID-19 syndrome were enrolled in the program for a duration of 40 weeks who received 5 intravenous infusions of 2 × 108 autologous HB-adMSCs each at week 0, 2, 6, 10 and 14 with a follow-up at week 18 and end of the study at week 40. Safety assessments included incidence of adverse and serious adverse events along with the laboratory measures of hematologic, hepatic, and renal function. Efficacy was examined by quality-of-life assessments, fatigue assessments, Visual analog scale (VAS) of symptoms and monitoring of respiration and oxygen saturation rates. RESULTS: VAS scores and Fatigue Assessment scores (FAS) showed significant improvements post-treatment (P = 0.0039, ES = 0.91) compared to baseline. Respiration rates and oxygen saturation levels that were within the normal range at the baseline remained unchanged at the end of the study (EOS). Paired comparison between baseline and EOS for short-form-36 health survey questionnaire (SF-36) scores also showed improved quality-of-life with significant improvements in individual SF-36 evaluations. Mostly mild AEs were reported during the study period with no incidence of serious AEs. Also, no detrimental effects in laboratory values were seen. CONCLUSIONS: The results of the expanded access program indicated that treatment with autologous HB-adMSCs resulted in significant improvements in the signs and symptoms associated with post-COVID-19 syndrome as assessed by VAS and FAS scores. Additionally, improvements in the patients' quality-of-life as demonstrated using SF-36 scores that also showed significant improvements in individual scaled scores. Overall, administration of multiple infusions of autologous HB-adMSCs is safe and efficacious for improvements in the quality-of life of patients with post-COVID-19 syndrome. TRIAL REGISTRATION: Clinical trial registration number: NCT04798066. Registered on March 15, 2021. ( https://clinicaltrials.gov/ct2/show/NCT04798066?term=hope+biosciences&cond=Post-COVID-19+Syndrome&draw=2&rank=2 ).

Long-term, repeated doses of intravenous autologous mesenchymal stem cells for a patient with Parkinson's disease: a case report.

Parkinson's disease (PD) is a neurodegenerative disease that involves the loss of dopaminergic neurons in the substantia nigra pars compacta of the basal ganglia. Clinically, patient presentation involves a combination of motor and non-motor symptoms characterized by progressive worsening over time and significant decreases in overall quality-of-life. Despite there being no fully restorative cure for PD, Mesenchymal Stem Cell (MSC) therapy offers promising therapeutic potential. Here, we report a case of a 77-year-old female, living with idiopathic Parkinson's Disease for over 17 years. The patient received multiple infusions of autologous Hope Biosciences adipose-derived MSCs (HB-adMSCs). A total of 26 infusion treatments of HB-adMSCs were administered over the course of ~2 years that resulted in marked improvements in her typical Parkinsonian symptoms, as demonstrated by the decreases in her UPDRS (Unified Parkinson's Disease Rating Scale) scores. Changes in clinical scores mirrored concurrent changes in regional brain metabolism as quantified by FDG-PET (Fluorodeoxyglucose-Positron Emission Tomography), compared to baseline. Long-term, multiple infusions of HB-adMSCs were safely tolerated by the patient without any serious adverse events. Further research is needed to evaluate the safety and efficacy of HB-adMSC therapy for the treatment of PD patients.

Functional recovery of a 41-year-old quadriplegic spinal cord injury patient following multiple intravenous infusions of autologous adipose-derived mesenchymal stem cells: a case report.

Spinal cord injury (SCI) is a debilitating disease with clinical manifestations ranging from incomplete neurological deficits affecting sensory and motor functions to complete paralysis. Recent advancements in stem cell research have elucidated the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of patients with SCI. Here, we present a case of a 41-year-old quadriplegic male individual who experienced a traumatic C-5 incomplete SCI, after slipping off a boat in Florida Keys on August 4, 2017. He was diagnosed with C5-C6 Grade 2 anterolisthesis with flexion teardrop fracture of the anterior C6 with jumped facet on the right and perched facet on the left at C5-C6 with spinal canal stenosis. On September 12, 2019, an Individual Expanded Access Protocol was approved for administration of multiple infusions of autologous, adipose-derived MSCs (adMSCs) for the treatment of this quadriplegic incomplete C5-6 SCI patient. Thirty-four (34) recurrent infusions each with 200 million cells were administered, over a period of ∼2.5 years, which resulted in significant improvements in his quality-of-life as demonstrated by substantial improvements in SCIM-III (Spinal Cord Independence Measure III) scores. Additionally, electromyography/nerve conduction velocity (EMG/NCV) studies showed improvements in the patient's motor and sensory function. No safety concerns were presented, and no serious adverse events were reported during the entire course of treatment. Multiple intravenous infusions of autologous HB-adMSCs for treatment of SCI demonstrated significant enhancements in the patient's neurological function with improved quality-of-life. Further research is needed to evaluate the results of this study.

Frequency-dependent effect of intravenous administration of human adipose-derived mesenchymal stem cell therapy for severe Systemic Lupus Erythematosus: A case report.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that involves abnormal activation of immune response, affecting multiple organs, including joints, kidneys, lungs, skin, and the hematopoietic system, thereby impairing their normal function. Despite there being no cure for SLE, Mesenchymal Stem Cell (MSC) therapy offers hope for SLE patients because of its potent role in immunomodulation. Here, we report a case of a 65-year-old female battling with SLE for almost 30 years and on a treatment regimen consisting of several medications. Given the level of immunosuppression associated with conventional SLE treatments, the subject was initially enrolled as a participant in a study protocol designed to provide immune protection against COVID-19. The subject received multiple infusions of autologous Hope Biosciences adipose-derived MSCs (HB-adMSCs) which significantly improved her SLE symptoms and functionality that led the patient's physician to discontinue her Rituximab regime. Based on her response to HB-adMSC therapy, the subject was approved to receive a set of nine infusion treatments to specifically treat her SLE symptoms. Over the course of ∼ one year, the first six infusions were given on a monthly basis, while the remaining three were administered bimonthly - each with a dose of 200 million HB-adMSCs. Since the beginning of the treatment, the subject showed remarkable improvements in her SLE symptoms, as demonstrated by changes in her SF-36 questionnaire responses, Visual Analog Scale (VAS) scores, and C-Reactive Protein (CRP) measurements; however, worsening of the symptoms was noted later during treatment course (when the frequency of infusions changed to bimonthly). Although the shift in remission-relapse cycle is not fully understood, however, the data suggest that treatment frequency might be the key player. No serious adverse events occurred during the entire treatment period. Further research is needed to evaluate the results of this study.