Taltirelin Hydrate

A 54-year-old male presented with a two-year history of recurrent syncope. Although he was treated with droxidopa and amezinium metilsulfate, his syncope was drug-resistant. Blood tests, cardiac evaluation and brain computed tomography (CT) were unremarkable. As his Schellong test was positive, orthostatic hypotension and syncope were the tentative diagnoses. Upon evaluating the patient neurologically while carefully avoiding syncope induction, mild cerebellar ataxia was observed. However, a brain magnetic resonance imaging (MRI) scan revealed a possible "cross sign" in the pons. Subsequent dopamine transporter single-photon emission computed tomography (DAT-SPECT) showed reduced uptake in the basal ganglia. Based on these findings, a clinical diagnosis of probable multiple system atrophy of the cerebellar type (MSA-C) was made, and treatment with taltirelin hydrate was initiated. This case underscores the importance of considering multiple system atrophy (MSA) in patients with persistent orthostatic hypotension and syncope, even before more obvious neurodegenerative symptoms emerge.

Combination therapy is a promising therapeutic strategy to enhance the efficacy of immune checkpoint blockade (ICB); however, predicting drugs for effective combination is challenging. Here we developed a general data-driven method called CM-Drug for screening compounds that can boost ICB treatment efficacy based on core and minor gene sets identified between responsive and nonresponsive samples in ICB therapy. The CM-Drug method was validated using melanoma and lung cancer mouse models, with combined therapeutic efficacy demonstrated in eight of nine predicted compounds. Among these compounds, taltirelin had the strongest synergistic effect. Mechanistic analysis and experimental verification demonstrated that taltirelin can stimulate CD8⁺ T cells and is mediated by the induction of thyroid-stimulating hormone. This study provides an effective and general method for predicting and evaluating drugs for combination therapy and identifies candidate compounds for future ICB combination therapy.