Arthur Burghes , Ph.D.
The Ohio State University
1645 Neil Avenue
Columbus, OH 43210
Phone: (614) 688-4579
Fax: (614) 292-4118
Education & Training:
Hammersmith Hospital, University London, Ph.D.
Hospital for Sick
Children, University of Toronto, Postdoctoral Fellow
The laboratory focuses primarily on two neuromuscular disorders, Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA). The primary focus now is developing animal models and identifying key mechanisms in SMA, with early studies in mapping and cloning the SMA gene and then subsequent characterization of the survival motor neurons genes and protein. We showed that SMN protein was reduced in SMA and that the severity of the phenotype was dependent on SMN2 copy number and the amount of SMN produced. My laboratory developed the SMA mice which are extensively used throughout the world, along with a series of additional mouse lines, to specially address factors in SMA such as the location and timing of SMN expression needed to correct SMA in mice. At this time, we also developed mice that overexpressed SMN mice with either 8 or 16 copies of SMN2. We have shown rescue of SMA mice with scAAV9-SMN as well as rescue with antisense morpholinos that restore full-length SMN production from SMN2. We have also developed a pig model of SMA. We are also studying the specific mechanism of why low levels of SMN gives rise to a motor neuron disease SMA as well as whether SMN levels influence muscle.
- Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, L'Italien J, Sproule DM, Wells C, Cardenas JA, Heitzer MD, Kaspar A, Corcoran S, Braun L, Likhite S, Miranda C, Meyer K, Foust KD, Burghes AHM, Kaspar BK. Single- Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713- 1722.
- Duque SI, Arnold WD, Odermatt P, Li X, Porensky PN, et al. A large animal model of Spinal Muscular Atrophy and correction of phenotype. Ann Neurol. 2014 Dec 16;PubMed PMID: 25516063.
- Porensky PN, Mitrpant C, McGovern VL, Bevan AK, Foust KD, et al. A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse. Hum Mol Genet. 2012 Apr 1;21(7):1625-38.
- Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, et al. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271- 4 PubMed PMID: 20190738; PubMed Central PMCID: PMC2889698.
- Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. (2010) “ Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN” Nat Biotechnol. 28:271-4.
- Butchbach ME, Singh J, Thorsteinsdóttir M, Saieva L, Slominski E, Thurmond J, Andrésson T, Zhang J, Edwards JD, Simard LR, Pellizzoni L, Jarecki J, Burghes AH, Gurney ME (2010) “Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy” Hum Mol Genet.19:454-67.
- McGovern VL, Gavrilina TO, Beattie CE and Burghes AH (2008) "Embryonic
motor axon development in the severe SMA mouse" Hum Mol Genet 17(18):2900-9.
- Burghes AH and Butchbach ME (2008) "Let all DNA vote: who are
- Thurmond J, Butchbach ME, Palomo M, Pease B, Rao M, Bedell L, Keyvan
M, Pai G, Mishra R, Haraldsson M, Andresson T, Bragason G, Thosteinsdottir
M, Bjornsson JM, Coovert DD, Burghes AH, Burney ME and Singh J (2008) "Synthesis
and biological evaluation of novel 2,4-diaminoquinazoline derivatives
as SMN2 promoter activators for the potential treatment of spinal muscular
atrophy" J Med Chem 51(3):449-69.
- Gavrilina TO, McGovern VL, Workman E, Crawford TO, Gogliotto RG,
DiDonato CJ, Monani UR, Morris GE and Burghes AH (2008) "Neuronal
SMN expression corrects spinal muscular atrophy in severe SMA mice
while muscle-specific SMN expression has no phenotypic effect" Hum
Mol Genet. 17(8):1063-75.
- McWhorter ML, Boon KL, Horan ES, Burghes AH and Beattie CE (2008) "The
SMN binding protein Gemin2 is not involved in motor axon outgrowth" Dev
My NCBI Link: https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/40596717/?sort=date&direction=ascending