@misc{10481/77701,
year = {2022},
month = {10},
url = {https://hdl.handle.net/10481/77701},
abstract = {Canine leishmaniosis is a challenge in veterinary medicine and no drug to date has achieved
parasite clearance in dogs. Histone deacetylase inhibitors are a drug class widely used in cancer
chemotherapy. We have successfully used O-alkyl hydroxamates (vorinostat derivatives) in the
treatment of a laboratory model of visceral leishmaniasis without showing toxicity. In order to
test the effectiveness of a particular compound, MTC-305, a parallel-group, randomized, singlecentre,
exploratory study was designed in naturally infected dogs. In this clinical trial, 18 dogs
were allocated into 3 groups and were treated with either meglumine antimoniate (104 mg SbV/kg),
MTC-305 (3.75 mg/kg) or a combination of both using a lower MTC-305 dose (1.5 mg/kg) through
a subcutaneous route for 2 treatment courses of 30 days, separated by a 30-day rest period. After
treatment, a follow-up time of 4 months was established. Parasite burden in bone marrow, lymph
node and peripheral blood were quantified through qPCR. Antibody titres were determined through
an immunofluorescence antibody test, and cytokine expression values were calculated through RTqPCR.
Treatment safety was evaluated through the assessment of haematological and biochemical
parameters in blood, weight, and gastrointestinal alterations. Assessment was carried out before,
between and after treatment series. Treatment with MTC-305 was effective at reducing parasite
burdens and improving the animals’ clinical picture. Dogs treated with this compound did not
present significant toxicity signs. These results were superior to those obtained using the reference
drug, meglumine antimoniate, in monotherapy. These results would support a broader clinical trial,
optimised dosage, and an expanded follow-up stage to confirm the efficacy of this drug.},
organization = {University of Granada},
organization = {Andalusian Government},
organization = {European Commission	B-CTS-270UGR18	
P20_00130},
publisher = {MDPI},
keywords = {Vorinostat derivatives},
keywords = {Canine leishmaniosis},
keywords = {Treatment},
keywords = {O-alkyl hydroxamates},
keywords = {Histone deacetylase inhibitors},
keywords = {Effectiveness},
keywords = {Safety},
title = {Effectiveness of an O-Alkyl Hydroxamate in Dogs with Naturally Acquired Canine Leishmaniosis: An Exploratory Clinical Trial},
doi = {10.3390/ani12192700},
author = {Corpas López, Victoriano and Díaz Sáez, Victoriano and Morillas Márquez, Francisco and Franco Montalbán, Francisco and Díaz Gavilán, Mónica and López-Viota Gallardo, Julián and López-Viota Gallardo, Margarita and Gómez Vidal, José Antonio and Martín Sánchez, Joaquina},
}