Early Transcriptional Activity of Vtr-297 - Results from an Ongoing Phase I Clinical Trial

Przychodzen, Bart; Mohrman, Michael; Brzezynski, Jennifer L.; Truslow, Sophia; Polymeropoulos, Christos; Polymeropoulos, Mihales

doi:10.1182/blood-2022-171079

Cited by 4 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If induction of NAT1 at onset is necessary to reduce disease progression, then strategies can be developed to induce NAT1 in the appropriate patient population. For example, the pan-histone deacetylase inhibitor VTR-297 is currently in clinical trials for hematologic malignancies (Przychodzen et al, 2022). The current study provides a strong foundation implicating NAT1 in ALS.…”

Section: Discussionmentioning

confidence: 75%

Arylamine N-acetyltransferase-1 reveals a subpopulation of ALS patients with altered metabolic capacity

Choudhury,

Allen,

Gill

et al. 2023

Preprint

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease characterised by metabolic changes at onset and throughout disease progression. Here, we investigate the role of arylamine N-acetyltransferase 1 (NAT1), a cytosolic protein associated with mitochondrial function, in ALS. We demonstrate that expression of the murine homolog (mNat2) increases in skeletal muscle of SODG93A mice, but not control animals, at onset of symptoms and remains elevated until end stage of the disease. Measurement of mitochondrial respiration in peripheral blood mononuclear cells of patients with ALS identified patient sub-populations with low and high metabolic potential, which was strongly associated with NAT1 activity. Those patients with high NAT1 activity had elevated basal respiration, ATP production, mitochondrial reserve, and aerobic glycolysis. NAT1 predicted increased whole body metabolic index, which may be clinically significant as these patients show increased functional decline and shorter survival. NAT1 may be a novel target in those patients with elevated activity

show abstract

Section: Discussionmentioning

confidence: 75%

Arylamine N-acetyltransferase-1 reveals a subpopulation of ALS patients with altered metabolic capacity

Choudhury,

Allen,

Gill

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Gut aging: A wane from the normal to repercussion and gerotherapeutic strategies

Abankwah,

Wang,

Wang

et al. 2024

Heliyon

View full text Add to dashboard Cite

Histone Deacetylases

Zheng,

Barczak,

Liu

et al. 2024

Epigenetic Drug Discovery

View full text Add to dashboard Cite

Histone deacetylases (HDAC) are enzymes that regulate biological activity through removal of acetyl groups from histones and non-histone proteins. A few HDAC inhibitors have been approved for use as anti-cancer agents, but their clinical uptake so far has been limited, presumably due to their adverse effect profiles. Consequently, a new generation of HDAC inhibitors has emerged with improved chemistry and pharmacological properties, optimised through mechanism of action and precision medicine strategies. In this chapter, we provide a brief history of HDAC biology and showcase a few notable HDAC inhibitors which have shown clinical promise in cancer and non-cancer indications. While interest in HDAC inhibitors has had its peaks and troughs, recent scientific discoveries intersecting epigenetics and immuno-oncology give us reason to believe that the therapeutic potential of HDAC inhibitors has yet to be fully realised. As the field advances, these next-generation HDAC inhibitors, coupled with their immunotherapy combinations, could very well become indispensable instruments in the fight against cancer and other diseases.

show abstract

Early Transcriptional Activity of Vtr-297 - Results from an Ongoing Phase I Clinical Trial

Cited by 4 publications

References 0 publications

Arylamine N-acetyltransferase-1 reveals a subpopulation of ALS patients with altered metabolic capacity

Arylamine N-acetyltransferase-1 reveals a subpopulation of ALS patients with altered metabolic capacity

Gut aging: A wane from the normal to repercussion and gerotherapeutic strategies

Histone Deacetylases

Contact Info

Product

Resources

About