Completed Projects

John Gerdes, PhD & Richard Bridges, PhD (Renewal)

University of Montana
Cerebral Positron Emission Tomography (PET) Imaging Agents for Monitoring ALS Therapy

Dr. Gerdes is the Packard Center's Boye Foundation Researcher for 2006 and 2008

The EAAT2 molecule is a cell membrane protein that removes excesses of the neurotransmitter glutamate. Abnormalities in EAAT2 quantity or in its behavior have long been tied to ALS. That could make the molecule a good indicator, or biomarker, of nervous system health. At some point, it could provide a way to measure if treatment is effective.
In our supported research, we hope to create a radioligand (tracer) molecule targeted to the EAAT2 protein. The tracer will enable us to detect the EAAT2 biomarker noninvasively within the brain and spinal cord, using positron emission tomography (PET) imaging. Our challenge comes in designing a tracer with a unique chemical structure ? a molecule with a high affinity for the EAAT2 target protein, one that can penetrate the brain?s natural barriers and that reaches specific central nervous system tissues. Ultimately, data from our studies may lead to a noninvasive way to monitor ALS in the clinic.

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Weichun Lin, PhD (Renewal)

UT Southwestern
Neuromuscular Synaptic Degeneration in Motoneuron Diseases

Weichun Lin’s team has created a novel transgenic mouse—based, in part, on a fairly newly-discovered, inheritable ALS mutation—that develops motor neuron disease with key features of the human disease. The mice become paralyzed at 5 months of age, and the paralysis progresses to the rest of the body within ten months. The specific cell error the model mice show should shed light on poorly-explored aspects of the ALS process, namely, events at the motor neuron synapse and those involving the cell’s system for removing damaged proteins. Lin’s grant supports his month by month study of motor neurons and synapses in this new model. He hopes to see how synaptic and conduction changes relate to outward signs of the disease.

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Maiken Nedergaard, MD, PhD (Renewal)

University of Rochester
Identification of early changes in astrocytic gene expression in a mouse model of ALS using FACS-Array analysis

Astrocytes are the most abundant central nervous system cell, yet their having a role in the progression of ALS has been discovered only recently. The star-shaped cells configure themselves into a close network, creating micro-environments where they contact neurons. These areas are critical for proper activity of neurons at synapses.
We plan to analyze the physical changes that astrocytes undergo throughout the progression of ALS, to determine how changes in this highly structured network, or syncytium, as it's called, influence motor neurons' susceptibility to cell death.
We also plan to study astrocytic genes that are misregulated in very early phases of the disease - before symptoms - in an attempt to identify early markers and the earliest-disrupted chemical pathways. This, we believe, could shed light on ways that astrocytes affect motor neuron cell death.

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