Don cleveland laboratory

Cleveland developed a pair of gene silencing therapies widely applicable in human neurodegenerative disease. He demonstrated that single dose infusion of such designer DNA drugs produces durable efficacy lasting more than three months throughout the entirety of the rodent and non-human nervous systems.

An initial application was for an inherited form of ALS and which entered clinical trial in In , an extension of this approach entered clinical trial for myotonic dystrophy. An additional application is in trial with a designer DNA drug chemically modified so that it is not recognized by RNase H and therefore does not stimulate RNA degradation but acts to correct an RNA splicing abnormality in spinal muscular atrophy, one of the most abundant genetic diseases of children.

Cleveland has pioneered additional gene silencing or gene replacement therapies for human nervous system disease using adenoassociated virus AAV. He and his colleagues have shown remarkably broad delivery within the nervous system and they are now developing this for human clinical trial expected to initiate in using AAV encoding a short hairpin RNA which acts with the RNA-induced silencing complex RISC to trigger degradation of the RNA encoded by a mutated superoxide dismutase gene causative of inherited ALS.

By generating mice that develop aneuploidy at high rates, Cleveland tested the year old hypothesis that aneuploidy drives tumorigenesis. Division of Medical Genetics. Search this site Search all sites. MENU Search. Cleveland's laboratory has focused in two major directions.

Molecular genetics and cell biology of mammalian chromosome movement and spindle assembly during mitosis: Our interests are in deciphering the mitotic checkpoint, major mechanism in mammals that insures delivery of every chromosome to each daughter cell during mitosis. They demonstrated that fatal motor neuron disease disease arises from toxicity of mutant superoxide dismutase SOD1 unrelated to its normal activity, thereby uncovering the mechanism underlying the major genetic form of Amyotrophic Lateral Sclerosis ALS.

Most importantly, they identified that motor neuron death in inherited ALS is non-cell autonomous, requiring mutant damage to both motor neurons and the neighboring supporting cells. This finding demonstrated the feasibility of stem cell replacement of non-neuronal cells as a viable therapy in ALS.