Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy.

Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients (tolerogenic dendritic cells, regulatory T cells, mesenchymal stem cells, and vaccination with T cells). Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis (EAE) model of MS in animals, in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.

Usefulness and correlation with clinical response of serum ustekinumab levels measured at 6 weeks versus 12 weeks.

BACKGROUND: Monitoring serum drug levels has been proposed as a useful tool for improving and personalizing the management of psoriasis. However, in the case of ustekinumab the usefulness of such monitoring was not demonstrated when drug levels were measured at week 12. OBJECTIVES: To evaluate the correlation of serum ustekinumab levels measured at weeks 6 and 12 with clinical response. METHODS: In a prospective cohort study, we enrolled patients with psoriasis treated with ustekinumab 45 mg every 12 weeks for at least 24 weeks. We measured serum ustekinumab levels at weeks 6 and 12 in each patient. Using the absolute PASI score, response to treatment was defined as optimal (≤1), excellent (≤3), appropriate (>3 and ≤5), or inappropriate (>5). RESULTS: About 54 serum samples from 27 patients were analyzed. No correlation was found between serum drug levels and absolute PASI at week 12. At week 6, an inverse linear correlation was found (p = .0001). Moreover, serum levels at week 6 were higher in patients with optimal, excellent and appropriate responses than in patients with an inappropriate response. CONCLUSIONS: Assessment of ustekinumab serum levels at week 6 could provide useful information in routine clinical practice.

Correlation between trough serum levels of adalimumab and absolute PASI score in a series of patients with psoriasis.

BACKGROUND: The possibility of monitoring serum drug levels has opened the door to optimising biologic therapy. To consolidate this advance, it is imperative to demonstrate an adequate correlation between serum drug levels and clinical course. OBJECTIVES: To investigate whether a correlation exists between adalimumab levels and clinical response measured as absolute PASI. METHODS: In a prospective cohort study, we enrolled 51 patients with psoriasis treated with adalimumab for at least 16 s. Patients received approved doses of adalimumab, but after 52 s the dosing interval could be modified according to clinical criteria. Excellent response was defined as PASI ≤3, appropriate response as PASI >3 and ≤5 and inappropriate response as PASI> 5. Correlations were calculated using Spearman's correlation test. RESULTS: A total of 92 serum samples from 51 patients were analysed. Significant differences were found in serum trough levels between patients achieving an excellent response (6.46 µg/mL), versus an appropriate (2.5 µg/mL) and an inappropriate response (2 µg/mL). The therapeutic range for adalimumab serum levels was from 3.30 to 7.30 µg/mL. CONCLUSIONS: We found an adequate correlation between drug serum levels and PASI scores. Monitoring of absolute PASI and serum levels can provide a personalised and cost-effective evaluation.

Clinical profile of lipid transfer protein syndrome in a mediterranean area

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Description of the novel HLA-DQB1*02:02:01:02 allele in a Spanish individual.

HLA-DQB1*02:02:01:02 has an intron sequences coming from a combination of DQB1*02:01:01 and DQB1*02:02:01:01.

Description of the novel HLA-DQB1*02:02:01:02 allele in a Spanish individual.

HLA-DQB1*02:02:01:02 has an intron sequences coming from a combination of DQB1*02:01:01 and DQB1*02:02:01:01.

Similar biological effect of high-dose oral versus intravenous methylprednisolone in multiple sclerosis relapses.

UNLABELLED: Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.