Final Program - American Society of Gene & Cell Therapy

Program Schedule, Wednesday, May 15, 2013
Wednesday, May 15, 2013
in historical context. Robust life-long phenotype correction has been achieved in adult mice after single dose treatment with AAVbased
vectors, and the translational challenges of moving towards clinical trials involving pediatric patients are currently being
addressed. These challenges include targeting the developing liver where hepatocellular proliferation leads to loss of episomal AAV
vector genomes and, depending on the therapeutic context, the possible need for vector re-administration to maintain effective
levels of transgene expression.
Stephen C. Strom, PhD
Placental Stem Cell Treatment of Liver Disease
Epithelial cells isolated from human amnion (hAE) have surface marker and gene expression proiles of pluripotent stem cells.
Our previous studies have shown that hAE mature liver genes when transplanted into the liver of mice. Accordingly hAE were
transplanted into the liver of iMSUD –mice, a useful model of the Maple Syrup Urine Disease. While untreated animals died at
weaning, treated animals survived and thrived on a normal protein diet out to adulthood and showed signiicant correction of
amino acid and neurotransmitter proiles. These results suggest that hAE cells could be a useful cellular therapy for metabolic liver
diseases.
Alessandra Bifi, MD
Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Treatment of Metachromatic
Leukodystrophy
Amit Nathwani, MD, PhD
AAV Mediated Gene Transfer for Hemophilia A
We have developed distinct approach for gene therapy of haemophilia A using adeno-associated virus (AAV) vectors which is based
on our successful strategy for gene therapy of haemophilia B. Data from our preclinical evaluation will be presented together with
an outline of Phase I/II trial design for Haemophilia A.
Scientific Symposium 102
8:00 am - 10:00 am
ROOM: BALLROOM B
Gene and Cell Therapies for Auditory and Olfactory Disorders
CO-CHAIRS: Jodi L. McBride, PhD and Anne Messer, PhD
SPEAKERS
Jeffrey R. Holt, PhD
Gene Therapy Strategies to Restore Sensory Function in the Inner Ear
Sensory transduction in hair cells of the inner ear is the fundamental irst step that converts auditory information into electrical
signals which are transmitted to the brain. Loss of sensory function in inner ear hair cells is the principle deicit in over sixty
forms of genetic deafness. To investigate gene therapy as a strategy for restoration of auditory function our lab is focused on viral
mediated delivery of wild-type Tmc1, mutations in which cause deafness in humans and mice. Tmc1 is expressed in hair cells and
preliminary data indicated that AAV re-introduction of wild-type Tmc1 into hair cells of deaf mice can restore sensory transduction
in vitro. Whether AAV-Tmc1 can restore sensory function in vivo is currently under investigation.
Lawrence Lustig, MD
AAV1-mediated Restoration of Hearing in the VGLUT3 Knockout Mouse
Mice lacking the vesicular glutamate transporter-3 (VGLUT3) are congenitally deaf due to loss of glutamate release at the inner hair
cell afferent synapse. Within two weeks of AAV1-VGLUT3 delivery, acoustic brainstem response (ABR) thresholds normalize, along
with partial rescue of the startle response. Lastly, we demonstrate partial reversal of the morphologic changes seen within the
afferent IHC ribbon synapse. These indings will be discussed and placed into the broader context of gene therapy for genetic forms
of hearing loss.
Jeffrey R. Martens, PhD
Gene Therapeutic Rescue of an Olfactory Ciliopathy
Olfactory dysfunction is a clinical manifestation of a growing class of human genetic diseases, termed ciliopathies. Despite
substantial progress made in identifying genes that cause ciliopathies, therapies for these disorders are not yet available to patients.
Here, we reported that odor detection can be restored to animals with a hypomorphic mutation in the gene encoding for the ciliary
protein IFT88 that results in the loss of cilia on differentiated olfactory sensory neurons (OSNs). These studies represent the irst in
vivo therapeutic treatment to reestablish cilia in a mammalian ciliopathy, and show that gene therapy is a viable curative option for
functional rescue of the complex cilia organelle in established differentiated cells.
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Final Program SALT LAKE CITY, UTAH May 15–18, 2013