| Principal Investigators | Project | Total Amount | Major Goals |
| Hiroshi Mitsumoto, M.D. Ruth Ottman, Ph.D. |
Epidemiology of Genetic and Environmental Interactions |
$66,000 |
Initiate a center-based genetic environmental study following the test-retest completion of the questionnaire.
Plan NYC or NYS ALS Registry and population-based epidemiology study. |
| Paul Gordon, M.D. |
Innovative multi-drug trial designs in ALS |
$45,000 |
Design multi-drug phase II trial with department of biostatistics
Review data on currently available medications with department of pharmacology
Meet with funding agencies to plan grant applications
Pilot innovative trial design |
| Hiroshi Mitsumoto, M.D.
Andreas Kottman, Ph.D. |
Genetic Basis of Variable Phenotypic Expression in ALS |
$60,000 (Carry over from 2004) |
Collect serum samples from ALS patients with and without prefrontal dementia and non-affected controls.
Determine the DNA sequence of the wolframin (wfs1) gene from 20 patients each with ALS or with ALS and prefrontal dementia and from 20 non-affected controls.
Characterize regulatory cis acting elements of the wfs1 locus. |
| Paul Gordon, M.D.
Michio Hirano, M.D.,
Ali Naini, Ph.D. |
Linkage Study to identify the novel modifier genes in familial ALS with SOD1 mutation |
$45,500 |
Complete DNA collection from family members
Characterize mouse model
Assess potential modifier genes
Perform linkage studies |
| Hiroshi Mitsumoto, M.D.
Center Staff |
DNA and autopsy tissue banking |
$57,750 |
To obtain NDA and tissue is imperative for the future ALS research.
This is to establish DNA and cell-line banking of all ALS patients.
Support the cost for body transportation in order to assist the family to give us permission to obtain autopsy in ALS
|
| Thomas Jessell, PhD |
1) Characterization of Motor Neuron Progenitor Cells; 2) directed differentiation of embryonic stem cells into Motor Neurons; and 3) the physiology and function ES cell-derived motor neurons in mammalian spinal cord
| $50,000 |
Optmize conditions for generation of defined motor neuron subtypes from mouse ES cells.
Develop a highly efficient method for generation of motor neuron subtypes from human ES cells (with C Henderson)
Define RNAs selectively transported into the axons of ES cell derived motor neurons (with H Wichterle)
Define conditions for evaluating the influence of mutant SOD expression on glial-motor neuron interactions (with S Przedborski)
|
| Christopher Henderson, Ph.D. |
Mechanisms of motor neuron cell death in ALS |
$75,000 |
To confirm the involvement of a novel, motor neuron-specific, cell death mechanism in motor neuron death in vivo
To test the effects of crossing mutant mice for Fas signaling with ALS mutant SOD mice
|
| Serge Perzedborksi, MD, PhD,
Thomas Jessell, PhD |
ER stress and NOGO pathway |
$70,000(Carrry over from 2004) |
We will test pharmacological and genetic strategies to improve the penetration of neurotic processes from stem cells differentiated into motor neurons into the white matter of the rats expressing mutant SOD1. This is an essential aspect toward using stem cells as a successful cell replacement strategy to repair the lower motor neuron pathway.
|
| William Dauer, MD |
Mechanisms of SOD1 regulation |
$52,570 |
Completed construction of transgenic and gene targeting constructs for inducible expression of mutant SOD1
Gene targeting and transgenic injections completed
Initial analysis of transgenic mice to identify founders
|
| Andreas H. Kottmann, PhD |
Function of wfs1 in the context of cranial and spinal motor neuron maintenance in mouse and in organotypic cultures
| $43,000 |
Establish organotypic spinal cord slice cultures from wfs1 loss of function animals to determine base
line measures for motor neuron survival and induction of ER stress responses as a function of wolframin
gene dosage and exposure to glutamate.
Establish embryonic stem cell lines from wfs1 loss of function animals.
|