A main focus of the Kaspar laboratory is centered on the mechanism(s) of neurodegeneration in Amyotrophic Lateral Sclerosis (ALS).  We employ rodent models of this disease to investigate various cell type involvements in disease onset and progression.  Furthermore, we are actively developing novel methods to deliver genes and therapies more efficiently to the nervous system and testing novel targets to combat this debilitating, lethal disease.

The laboratory also investigates the biological control of embryonic and adult derived stem cells.  Our current studies with stem cells are evaluating cell cycle regulation along with developing methods for intricate control of differentiation to defined cellular phenotypes, such as complex motor neurons.   

Finally, our laboratory works on muscle enhancing strategies in order to combat musculoskeletal disorders.  We have identified that follistatin is a potent antagonist of myostatin, and when delivered by a one-time gene delivery to skeletal muscle, enhances muscle size and mass.  Interestingly, our work has demonstrated that follistatin reduces the inflammatory environment in dystrophic muscles and induces improvements in functional strength in rodent models of Duchene Muscular Dystrophy.  We are currently involved with developing a human clinical trial for Inclusion Body Myositis with Dr. Jerry Mendell.

Kevin D Foust, Xueyong Wang, Vicki L McGovern, Lyndsey Braun, Adam K Bevan, Amanda M Haidet, Thanh T Le, Pablo R Morales, Mark M Rich, Arthur H M Burghes, & Brian K Kaspar. Rescue of spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nature Biotech 2010; 28(3):271-4

Kaspar RW, Wills CE, Kaspar BK. Gene therapy and informed consent decision making: nursing research directions. Biol Res Nurs. 2009 July;11(1):98-107.

Hester M, Song SW, Miranda C, Eagle A, Schwartz P, Kaspar BK. Two Factor Reprogramming of Human Neural Stem Cells into Pluripotency, PLoS One. 2009, 4(9):e7044.

Hester ME, Foust KD, Kaspar RW, Kaspar BK. AAV as a gene transfer vector for the treatment of neurological disorders: novel treatment thoughts for ALS. Curr Gene Ther. 2009 Oct;9(5):428-33.

Janaiah Kota, Chalonda R. Handy, Amanda M. Haidet, Chrystal L. Montgomery, Amy Eagle, Louise R. Rodino-Klapac, Danielle Tucker, Christopher J. Shilling, Walter R. Therlfall, Christopher M. Walker, Steven E. Weisbrode, Paul M. L. Janssen, K. Reed Clark, Zarife Sahenk, Jerry R. Mendell, Brian K. Kaspar. Follistatin Gene Delivery Enhances Muscle Growth and Strength in nonhuman primates. Science Translational Medicine, 2009 Nov 11;1(6) 6ra15

Kevin D. Foust and Brian K. Kaspar. Over the barrier and through the blood To CNS delivery we go. Cell Cycle. 2009 8(24)16-17

Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve. 2009 Mar;39(3):283-296.

Excoffon KJ, Koerber JT, Dickey DD, Murtha M, Keshavjee S, Kaspar BK, Zabner J, Schaffer DV.   Directed evolution of adeno-associated virus to an infectious respiratory virus. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3865-70

Miller TM, Smith RA, Kordasiewicz H, Kaspar BK. Gene-targeted therapies for the central nervous system. Arch Neurol. 2008 Apr;65(4):447-51. Epub 2008 Feb 11

McCrate ME, Kaspar BK. Physical activity and neuroprotection in amyotrophic lateral sclerosis. Neuromolecular Med. 2008;10(2):108-17.

Haidet AM, Rizo L, Handy C, Umapathi P, Eagle A, Shilling C, Boue D, Martin PT, Sahenk Z, Mendell JR, Kaspar BK. Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4318-22.

Rodino-Klapac LR, Chicoine LG, Kaspar BK, Mendell JR. Gene therapy for duchenne muscular dystrophy: expectations and challenges. Arch Neurol. 2007 Sep;64(9):1236-41.