3.8.17

HDAC6 INHIBITION EFFECTIVELY REVERSES CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY

Chemotherapy-induced peripheral neuropathy is one of the most common dose-limiting side effects of cancer treatment. Currently, there is no Food and Drug Administration–approved treatment available. Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase whose function includes regulation of α-tubulin–dependent intracellular mitochondrial transport. Here, we examined the effect of HDAC6 inhibition on established cisplatin-induced peripheral neuropathy. READ MORE


1.6.17

SELECTIVE INHIBITORS OF HISTONE DEACETYLASES 1 AND 2 SYNERGIZE WITH AZACITIDINE IN ACUTE MYELOID LEUKEMIA

Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain poor, highlighting the need for novel treatment options. READ MORE 


12.6.16

DEVELOPMENT OF IMPROVED HDAC6 INHIBITORS AS PHARMACOLOGICAL THERAPY FOR AXONAL CHARCOT–MARIE–TOOTH DISEASE

Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy, with an estimated prevalence of 1 in 2500. Currently, there is no curative treatment available. Recently, we identified histone deacetylase 6 (HDAC6), which deacetylates α-tubulin, as a potential therapeutic target in axonal CMT (CMT2). READ MORE


4.13.16

CHEMICAL INHIBITION OF HISTONE DEACETYLASES 1 AND 2 INDUCES FETAL HEMOGLOBIN THROUGH ACTIVATION OF GATA2

Therapeutic intervention aimed at reactivation of fetal hemoglobin protein (HbF) is a promising approach for ameliorating sickle cell disease (SCD) and β-thalassemia. Previous studies showed genetic knockdown of histone deacetylase (HDAC) 1 or 2 is sufficient to induce HbF. Here we show that ACY-957, a selective chemical inhibitor of HDAC1 and 2 (HDAC1/2), elicits a dose and time dependent induction of γ-globin mRNA (HBG) and HbF in cultured primary cells derived from healthy individuals and sickle cell patients. READ MORE