Lublin FD, Bowen JD, Huddlestone J, Kremenchutzky M, Carpenter A, Corboy JR, Freedman MS, Krupp L, Paulo C, Hariri RJ, Fischkoff SA. Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: A randomized, placebo-controlled, multiple-dose study.Mult Scler Relat Disord. 2014 3:696-704.
BACKGROUND: Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis.
OBJECTIVE:This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis.
METHODS:This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse.
RESULTS: Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score >0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included headache, fatigue, infusion site reactions, and urinary tract infection.
CONCLUSION:PDA-001 infusions were safe and well tolerated in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosispatients. No paradoxical worsening of lesion counts was noted with either dose.
So this is a safety study of a stem cell and based on the data it did not make MS worse but it did not provide enough information to determine whether it made things better. This cell comes from someone elses placenta and so if it became a useful cell in the future it may been to protected against tissue rejection that could happen. There will be a number of papers surfacing about stem cells notably mesenchymal-stem cells. What will happen? I am not sure but I have a concern. Based on animal studies these mesenchymal cells induce no or marginal immunosuppressive activity. It this is all they do it will be an expensive way to cause immunosuppression and in the majority of cases you can achieve much better results with current DMT. However what we want from these cells is the re-creation of myelination and even regrowth of nerves. To date in animals this has been marginal and is problematic due to poor penetration of the cells to get into the CNS if administered systemically. Then they have to differentiate into myelinating cells, which the oligodendrocyte precursors already present in the CNS are not doing.
So whilst stem cells hold much promise, we have to be realistic about what we are likely to achieve and not get our hopes too high
Labels: Placental stem cells