Mogamulizumab for Treatment of Human T-lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis: A Single-Center US-based Series.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurological condition characterized by progressive myelopathic symptoms including spasticity, pain, weakness, and urinary symptoms, without proven treatments. Mogamulizumab (MOG) is a monoclonal antibody that binds CCR4 and leads to the clearance of HTLV-1-infected CCR4+ cells. A phase 1-2a study in Japan evaluated MOG for the treatment of HAM/TSP and reported decreases in HTLV-1 proviral load and neuroinflammatory markers, with clinical improvement in some participants. METHODS: We administered MOG 0.1 mg/kg every 8 weeks to individuals with HAM/TSP as a compassionate and palliative treatment. Patients who received MOG had (1) a positive peripheral HTLV-1 antibody, (2) progressive myelopathic symptoms, and (3) a diagnosis of HAM/TSP. RESULTS: Four female patients, ages 45-68, received MOG (range, 2-6 infusions) between 1 November 2019 and 30 November 2022. Two patients with <3 years of symptoms had milder disease, with Osame scores <4. The other 2, with >7 years of symptoms, had Osame scores >5. One patient, with 6 total treatments, received dose-reduced MOG after she developed a rash at the initial dose. The 2 patients with milder baseline disease reported symptomatic improvement and saw reductions in Osame and/or modified Ashworth scale scores during follow-up. The other 2 patients showed no improvement. All 4 developed rashes after receiving MOG-a treatment-limiting event in some cases. CONCLUSIONS: Clinical trials are needed including diverse patient populations to assess the potential role of MOG for HAM/TSP. Our findings may help inform the development of these trials.

Sources, sinks, and exposure pathways of lead in urban garden soil.

The chemistry of Pb in urban soil must be understood in order to limit human exposure to Pb in soil and produce and to implement remediation schemes. In inner-city gardens where Pb contamination is prevalent and financial resources are limited, it is critical to identify the variables that control Pb bioavailability. Field-portable X-ray fluorescence was used to measure Pb in 103 urban gardens in Roxbury and Dorchester, MA, and 88% were found to contain Pb above the USEPA reportable limit of 400 mug g(-1). Phosphorus, iron, loss on ignition, and pH data were collected, Pb-bearing phases were identified by X-ray diffraction, and Pb isotopes were measured using inductively coupled plasma mass spectrometry. Four test crops were grown both in situ and in Roxbury soil in a greenhouse, and plant tissue was analyzed for Pb uptake by polarized energy-dispersive X-ray fluorescence. Variation at the neighborhood scale in soil mineralogical and chemical characteristics suggests that the bioavailable fraction of Pb in gardens is site specific. Based on Pb isotope analysis, two historical Pb sources appear to dominate the inventory of Pb in Roxbury gardens: leaded gasoline ((207) Pb/(206) Pb = 0.827) and Pb-based paint ((207)Pb/(206) Pb = 0.867). Nearly 70% of the samples analyzed can be isotopically described by mixing these two end members, with Pb-based paint contributing 40 to 80% of the mass balance. A simplified urban human exposure model suggests that the consumption of produce from urban gardens is equivalent to approximately 10 to 25% of children's daily exposure from tap water. Furthermore, analysis of over 60 samples of plant tissue from the four test species suggests that in these urban gardens unamended phytoremediation is an inadequate tool for decreasing soil Pb.