Taylor HR (1990) Int Ophthalmol "Onchocerciasis."

Taylor HR

[Int Ophthalmol, 1990]

Onchocerciasis is a devastating blinding disease caused by the parasite Onchocerca volvulus that infects about 80 million people, causing blindness and visual impairment in 1-2 million people. In hyperendemic areas, more than half of the population will become blind from onchocerciasis before they die. Blindness is the most important effect of the disease and results, in part, from direct invasion of the eye by microfilariae. The recent development of ivermectin has revolutionized our ability to treat this disease. An annual oral dose of only 150 mg/kg completely suppresses the disease manifestations. Programs for the community-based mass distribution of ivermectin are now being conducted and promise to control this major blinding scourge.

Taylor HR (1990) Acta Leiden "Ivermectin treatment of ocular onchocerciasis."

Taylor HR

[Acta Leiden, 1990]

Ivermectin, a recently developed macrocyclic lactone with broad antiparasitic activity, has been shown by a series of clinical trials to be safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/Kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement, although ivermectin has no known long-lasting effects on the adult worms. With treatment there is no significant exacerbation of either anterior or posterior segment eye disease even in those with severe ocular disease. Treatment leads to a marked and prolonged improvement in ocular status. Because of its safety and efficacy, ivermectin can be used on a mass scale and promises to revolutionize the treatment of onchocerciasis.

Taylor HR et al. (1989) Am J Trop Med Hyg "The status of ivermectin in the treatment of human onchocerciasis."

Greene BM, Taylor HR

[Am J Trop Med Hyg, 1989]

Ivermectin is a macrocyclic lactone that has widespread antiparasitic activity. Numerous clinical trials have shown that ivermectin is safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction, as is seen with diethylcarbamazine treatment. The drug temporarily interrupts production of microfilaria but has not known long-lasting effects on the adult worms. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement. At this dose, ivermectin causes minimal side effects and is sufficiently free of severe reactions to be used on a mass scale. It promises to revolutionize the treatment of onchocerciasis.

Adelman CA et al. (2010) FEBS Lett "Metabolism of postsynaptic recombination intermediates."

Boulton SJ, Adelman CA

[FEBS Lett, 2010]

DNA double strand breaks and blocked or collapsed DNA replication forks are potentially genotoxic lesions that can result in deletions, aneuploidy or cell death. Homologous recombination (HR) is an essential process employed during repair of these forms of damage. HR allows for accurate restoration of the damaged DNA through use of a homologous template for repair. Although inroads have been made towards understanding the mechanisms of HR, ambiguity still surrounds aspects of the process. Until recently, relatively little was known concerning metabolism of postsynaptic RAD51 filaments or how synthesis dependent strand annealing intermediates are processed. This review discusses recent findings implicating RTEL1, HELQ and the Caenorhabditis elegans RAD51 paralog RFS-1 in post-strand exchange events during HR.

Belan O et al. (2021) Curr Opin Genet Dev "Mechanism of mitotic recombination: insights from C. elegans."

Boulton SJ, Anand R, Belan O

[Curr Opin Genet Dev, 2021]

Homologous recombination (HR) plays a critical role in largely error-free repair of mitotic and meiotic DNA double-strand breaks (DSBs). DSBs are one of the most deleterious DNA lesions, which are repaired by non-homologous end joining (NHEJ), homologous recombination (HR) or, if compromised, micro-homology mediated end joining (MMEJ). If left unrepaired, DSBs can lead to cell death or if repaired incorrectly can result in chromosome rearrangements that drive cancer development. Here, we describe recent advances in the field of mitotic HR made using Caenorhabditis elegans roundworm, as a model system.

van Kregten M et al. (2014) Exp Cell Res "The repair of G-quadruplex-induced DNA damage."

Tijsterman M, van Kregten M

[Exp Cell Res, 2014]

G4 DNA motifs, which can form stable secondary structures called G-quadruplexes, are ubiquitous in eukaryotic genomes, and have been shown to cause genomic instability. Specialized helicases that unwind G-quadruplexes in vitro have been identified, and they have been shown to prevent genetic instability in vivo. In the absence of these helicases, G-quadruplexes can persist and cause replication fork stalling and collapse. Translesion synthesis (TLS) and homologous recombination (HR) have been proposed to play a role in the repair of this damage, but recently it was found in the nematode Caenorhabditis elegans that G4-induced genome alterations are generated by an error-prone repair mechanism that is dependent on the A-family polymerase Theta (Pol ). Current data point towards a scenario where DNA replication blocked at G-quadruplexes causes DNA double strand breaks (DSBs), and where the choice of repair pathway that can act on these breaks dictates the nature of genomic alterations that are observed in various organisms.