fumarates and Weight-Loss

To determine whether changing from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing regimen is correlated with weight changes in a human immunodeficiency virus (HIV)-positive adult cohort.. Retrospective analysis was conducted of data gathered from routine care in a university hospital in Munich, Germany, between July 2015 and June 2017. Data from patients' charts were extracted and a two-step approach was applied. First, weight/BMI progression within 1 year after initiation of either TDF or TAF was compared. Subsequently, weight measurements within subjects changing from a TDF- to a TAF-containing antiretroviral regimen were analyzed by means of a repeated measurements general linear model.. After 360 days of initiating TAF, patients showed a mean (± standard deviation) percentual weight increase of 3.17 ± 0.21, whereas after 360 days of initiating TDF, patients only showed a mean (± standard deviation) percentual weight increase of 0.55 ± 0.17. The repeated measurements general linear model for within-subjects design showed a statistically significant correlation in weight after changing from a TDF to a TAF containing antiretroviral regimen. The weight difference between the two measurements while on TDF was not statistically significant, but every measure after switching to TAF was significantly higher than the previous.. Changing from a TDF- to a TAF-containing regimen is correlated with weight gain in this retrospectively analyzed real-world cohort in Munich, Germany.

Topics: Adenine; Adult; Alanine; Anti-HIV Agents; Cohort Studies; Female; Fumarates; Germany; HIV Seropositivity; Hospitals, University; Humans; Male; Middle Aged; Retrospective Studies; Tenofovir; Weight Gain; Weight Loss

Huntington's disease (HD) is an autosomal dominantly inherited progressive neurodegenerative disease. The exact sequel of events finally resulting in neurodegeneration is only partially understood and there is no established protective treatment so far. Some lines of evidence speak for the contribution of oxidative stress to neuronal tissue damage. The fumaric acid ester dimethylfumarate (DMF) is a new disease modifying therapy currently in phase III studies for relapsing-remitting multiple sclerosis. DMF potentially exerts neuroprotective effects via induction of the transcription factor "nuclear factor E2-related factor 2" (Nrf2) and detoxification pathways. Thus, we investigated here the therapeutic efficacy of DMF in R6/2 and YAC128 HD transgenic mice which mimic many aspects of HD and are characterized by an enhanced generation of free radicals in neurons. Treatment with DMF significantly prevented weight loss in R6/2 mice between postnatal days 80-90. At the same time, DMF treatment led to an attenuated motor impairment as measured by the clasping score. Average survival in the DMF group was 100.5 days vs. 94.0 days in the placebo group. In the histological analysis on day 80, DMF treatment resulted in a significant preservation of morphologically intact neurons in the striatum as well as in the motor cortex. DMF treatment resulted in an increased Nrf2 immunoreactivity in neuronal subpopulations, but not in astrocytes. These beneficial effects were corroborated in YAC128 mice which, after one year of DMF treatment, also displayed reduced dyskinesia as well as a preservation of neurons. In conclusion, DMF may exert beneficial effects in mouse models of HD. Given its excellent side effect profile, further studies with DMF as new therapeutic approach in HD and other neurodegenerative diseases are warranted.

Topics: Animals; Dimethyl Fumarate; Disease Models, Animal; Fumarates; Huntington Disease; Mice; Mice, Transgenic; Motor Activity; Neuroprotective Agents; Survival Rate; Treatment Outcome; Weight Loss