Cord Tissue Mesenchymal Stem Cells in the treatment of Autism Spectrum Disorders
- Dr. Kouzi
Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder
Jessica Sun1, Geraldine Dawson2, Lauren Franz2, Jill Howard2, Colleen McLaughlin1, Bethany Kistler1, Barbara Waters-Pick3, Norin Meadows1, Jesse Troy1, Joanne Kurtzberg1
1The Marcus Center for Cellular Cures, Duke University, Durham, North Carolina
2Duke Center for Autism and Brain Development, Duke University, Durham, North Carolina
3Stem Cell Transplant Laboratory, Duke University, Durham, North Carolina
Ongoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open-label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT-MSCs), a third-party MSC product manufacturedfrom unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 10(6) cells per kilogram at 2-month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT-MSCs were well tolerated. Five participants developed new class I anti-human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT-MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASDspecific measures. Manufacturing and administration of hCT-MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo-controlled clinical trial.
STEM CELLS Transl Med. 2020;1–10. DOI: 10.1002/sctm.19-0434
New clinical trial by using mesenchymal stem cells in the treatment of Covid 19 lung failure
- Dr. Kouzi
Reports of 83% survival in ventilator-dependent COVID-19 patients following mesenchymal stem cell therapy
Australian stem cell company Mesoblast Ltd. announced an 83% survival rate in ventilator-dependent COVID-19 patients with moderate to severe acute respiratory distress syndrome (ARDS) treated at New York’s Mount Sinai Hospital with allogeneic mesenchymal stem cells.
Nine of the 12 treated patients (75%) have successfully come off ventilator support within 10 days following two infusions of remestemcel-L.
“Once you’re ventilated when you have acute respiratory distress syndrome in the lungs, your likelihood of coming off a ventilator is 9%, and your survival is 12%,” Mesoblast CEO Silviu Itescu told BioWorld.
In contrast, only 9%, or 38 of 445 ventilator-dependent COVID-19 patients at a major hospital network in New York were able to come off ventilator support when treated with standard of care during the same March to April period.
Moreover, there was 88% mortality with only 12% survival (38/320) among ventilator-dependent COVID-19 patients at a second major hospital network in New York during the same period.
Those poor outcomes are consistent with earlier published data from China where mortality rates of over 80% were reported in patients with COVID-19 and moderate to severe ARDS.
At this time, 7 of the 12 treated patients have been discharged from the hospital. Patients received a variety of experimental agents prior to remestemcel-L. All patients were treated under an emergency IND or expanded access protocol at Mount Sinai.
Under the protocol, patients come into intensive care and received standard-of-care treatment. Once they were intubated on a ventilator, they were treated within 72 hours with two infusions of Mesoblast’s remestemcel-L cells within five days.
A bright light among dismal options
“What’s exciting is that our patients in the same epicenter of this disease with the same treatment everyone else is getting, suddenly 75% are coming off of ventilators within 10 days, and we’ve got 83% survival,” Itescu said.
The compassionate use treatment experience has informed the design of the clinical protocol for a randomized, placebo-controlled phase II/III trial of remestemcel-L in ventilator-dependent COVID-19 moderate to severe ARDS patients across North America.
The FDA has approved the same protocol for the phase II/III trial, and it will be powered so that results will be “self-evident,” Itescu said, noting that the trial will begin “imminently” in 20 to 30 sites across the U.S..
“We’ll know very fast if we’re seeing the same survival benefit in a randomized trial,” the CEO said.
“What people are dying of is acute respiratory distress syndrome, which is the body’s immune response to the virus in the lungs, and the immune system goes haywire, and in its battle with the virus it overreacts and causes severe damage to the lungs,” he said.
The stem cell therapy is currently being reviewed by the FDA for potential approval in the treatment of children with steroid-refractory acute graft-vs.-host disease (aGVHD). The clinical data submitted with the BLA showed a survival rate of 79% compared to an expected 30% survival rate in the pediatric phase III trial in aGVHD.