|
|
KASPAR LABORATORY
The main focus of the Kaspar laboratory is centered on the mechanism(s) of neurodegeneration in Amyotrophic Lateral Sclerosis (ALS) and the design and utilization of novel therapies to combat this debilitating, lethal disease. The underlying cause for ALS remains highly elusive and there is no known cure. There have been few effective therapies that have emerged to impede the progression of the disease in the ALS mouse model, and ironically, only a few of these therapies have translated their beneficial effects to human beings. Specifically, the lab is skilled in utilizing adeno-associated viral (AAV) gene therapy to deliver genes to all areas of the central nervous system (CNS). Dr. Kaspar has demonstrated that AAV-mediated delivery of IGF-1 to the spinal cord can prolong survival of a mouse model of ALS that is equivalent to adding years to the lives of ALS patients. Currently, clinical trials are being developed to translate this discovery into a therapeutic for ALS patients. Other neurotrophins are being investigated for their neuroprotective characteristics as well as novel delivery strategies are being pursued to target the CNS more efficiently in the treatment of ALS.
In addition to delivering neurotrophic support such as IGF-1 to the spinal cord by AAV, the Kaspar laboratory is developing strategies to differentiate motor neurons from adult neural progenitor cells. Adult neural progenitors exhibit stem cell characteristics as demonstrated by their multipotentiality and self-renewal. Unlike embryonic stem cells, there is no controversy related to these cells since they are isolated from the adult nervous system. We are currently designing procedures to transplant these differentiated motor neurons into the spinal cords of ALS mice in efforts to establish a cell replacement therapeutic for ALS.
|
| Education |
| 2004 |
|
Postdoc |
|
Gene Therapy/Neuroscience |
|
Salk Institute for Biological Studies, La Jolla, CA |
| 2003 |
|
Ph.D. |
|
Molecular Pathology |
|
University of California, San Diego, San Diego, CA |
KASPAR LABORATORY STAFF
|
Principal Investigator:
Brian K. Kaspar, Ph.D.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Selected Publications |
| Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009 Jan;27(1):59-65 PubMed ID: 19098898 |
| 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 PubMed ID: 18268183 |
| McCrate ME, Kaspar BK. Physical activity and neuroprotection in amyotrophic lateral sclerosis. Neuromolecular Med. 2008;10(2):108-17. Epub 2008 Feb 20 PubMed ID: 18286388 |
| 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. Epub 2008 Mar 11 PubMed ID: 18334646 |
| Brian K Kaspar, Mesenchymal Stem Cells as Trojan Horses for GDNF Delivery in ALS. Molecular Therapy, Vol. 16(12):2008. PubMed ID: 19032270 |
| Kim ML, Chandrasekharan K, Glass M, Shi S, Stahl MC, Kaspar B, Stanley P, Martin PT. O-funocylation of muscle agrin determines its ability to cluster acetylcholine receptors, Mol Cell Neurosci, 2008 Nov;39(3):452-64 PubMed ID: 18775496 |
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. PubMed ID: 17846262 |
| Maheshri N, Koerber JT, Kaspar BK, Schaffer DV. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors.Nature Biotechnology, 2006. Feb 24; 198-204. PubMed ID: 16429148 |
| Timothy M. Miller, Soo H. Kim, Mark Hester, Priya Umapathi, Hannah Arnson, Lisa Rizo, Jerry Mendell, Fred H. Gage, Don W. Cleveland, Brian K. Kaspar. Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19546-51. Epub 2006 Dec 12. PubMed ID: 17164329 |
| Kaspar, BK, Frost LM, Christian L, Umapathi P, Gage FH. Synergy of Insulin-like Growth Factor-1 and Exercise in Amyotrophic Lateral Sclerosis. Annals of Neurology. 2005 May 57 649-655. PubMed ID: 15852403 |
| Hsieh J, Aimone JB, Kaspar BK, Kuwabara T, Nakashima K and Gage FH. IGF-1 instructs multipotent adult neural progenitor cells to become oligodenndrocytes. Jrnl of Cell Biology 164: 111-122, 2004. PubMed ID: 14709544 |
| Kaspar BK, Llado J, Sherkat N, Rothstein JD and Gage FH. Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 839-842, 2003. PubMed ID: 12907804 |
| Lai K, Kaspar BK, Gage FH and Schaffer DV. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci 6(1): 21-27, 2003. PubMed ID: 12469128 |
| Kaspar BK, Vissel B, Bengoechea T, Crone S, Randolph-Moore L, Muller R, Brandon EP, Schaffer D, Verma IM, Lee KF, Heinemann SF and Gage FH. Adeno-associated virus effectively mediates conditional gene modification in the brain. Proc Natl Acad Sci 99(4): 2320-2325, 2002. PubMed ID: 11842206 |
| Kaspar BK, Erickson D, Schaffer D, Hinh L, Gage FH and Peterson DA. Targeted retrograde gene delivery for neuronal protection. Mol Ther 5(1): 50-56, 2002. PubMed ID: 11786045 |
| Lie DC, Dziewczapolski G, Willhoite AR, Kaspar BK, Shults CW and Gage FH. The adult substantia nigra contains progenitor cells with neurogenic potential. J Neurosci 22(15): 6639-6649, 2002. PubMed ID: 12151543 |
| Palmer TD, Schwartz PH, Taupin P, Kaspar B, Stein SA and Gage FH. Cell culture. Progenitor cells from human brain after death. Nature 411(6833): 42-43, 2001. PubMed ID: 11333968 |
|
