The New England journal of medicine
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Randomized Controlled Trial Comparative Study
Inhibition of CD40L with Frexalimab in Multiple Sclerosis.
The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis. ⋯ In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628.).
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A 67-year-old woman with a history of obesity, chronic low back pain, and recurrent episodes of major depression presents with mild depressive symptoms of more than 2 years’ duration, with worsening symptoms over the past 4 months. She was receiving sertraline at a stable dose of 100 mg per day until 3 months ago, when she initially presented for her worsening depressive symptoms. ⋯ Her nine-question Patient Health Questionnaire (PHQ-9) score is 17 (on a scale of 0 to 27, with higher scores indicating greater severity of depressive symptoms). How would you evaluate and treat this patient?
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Wolman's disease, a severe form of lysosomal acid lipase deficiency, leads to pathologic lipid accumulation in the liver and gut that, without treatment, is fatal in infancy. Although continued enzyme-replacement therapy (ERT) in combination with dietary fat restriction prolongs life, its therapeutic effect may wane over time. ⋯ Here we describe an infant with Wolman's disease who received high-dose ERT, together with dietary fat restriction and rituximab-based B-cell depletion, as a bridge to early HSCT. At 32 months, the infant was independent of ERT and disease-free, with 100% donor chimerism in the peripheral blood.