Spinal Cord Injuries and Congenital or Acquired Disease Processes
Research Program
The 91st General Assembly enacted legislation (HB 218 and HB 302, 2001) to provide support for a program of research projects that promote and advance knowledge in the areas of spinal cord injuries and congenital or acquired disease processes. As part of this legislation, there was created in the state treasury a “Spinal Cord Injury Fund” from which annual appropriations are to be made for the use of the Board of Curators of the University of Missouri. The primary source of money for this fund is a surcharge of two dollars levied on certain costs in criminal cases including violations of any county ordinance or any violation of criminal or traffic laws of the state.
The research grants funded by these appropriations are to be awarded by the Board of Curators to investigators who are affiliated with a public or private educational, health care, voluntary health association or research institution, based on the recommendations of an Advisory Board appointed by the Board of Curators for this purpose. Individual awards (originally limited to $50,000 per year, but increased in 2010 to $250,000 per year) shall expire at the end of one or two years. The objective of the grants is to obtain preliminary data to test hypotheses and to enable investigators to develop subsequent competitive applications for long-term funding from other sources. The research projects are to be conducted in Missouri.
“Congenital” spinal cord abnormalities include birth defects affecting the spinal cord such as spina bifida. In addition to traumatic injuries to the spinal cord that lead to paralysis, “acquired” abnormalities could include Friedreich’s ataxia, which manifests itself in teenage years and appears to run in families, and paralysis due to multiple sclerosis, polio, etc. Approximately 450,000 people in the United States have sustained traumatic spinal cord injuries (SCI), with approximately 11,000 new cases of SCI in the US every year. The majority (78%) of SCI victims are males. Most of the injuries result from motor vehicle accidents (50%), falls (24%), violence (11%), or sports injuries (9%).
The action requested of the Board is to approve funding for one research proposal approved by the Spinal Cord Injury Advisory Board.
Recommended Action -Spinal Cord Injuries and Congenital or Acquired Disease Processes Research Program Proposal
It was recommended by Interim Vice President of Academic Affairs, Robert W. Schwartz, Ph.D., endorsed by Interim President Michael A. Middleton, recommended by the Academic, Student and External Affairs Committee, moved by Curator ______, and seconded by Curator ______, that the following actions be approved:
that the research proposals approved by the Spinal Cord Injuries Research Program Advisory Board be approved as presented on the following pages.
Roll call vote of the Committee:YESNO
Curator Cupps
Curator Phillips
Curator Snowden
Curator Steelman
The motion ______.
Roll call vote of the Board:YESNO
Curator Cupps
Curator Graham
Curator Henrickson
Curator Phillips
Curator Snowden
Curator Steelman
The motion ______.
SPINAL CORD INJURIES AND CONGENITAL OR ACQUIRED DISEASE PROCESSES RESEARCH PROGRAM
PROPOSAL RECOMMENDED FOR FUNDING
2016
- Pre-clinical development of E1-targeting ASOs in SMA
Christian Lorson
Professor
University of Missouri-Columbia
Total funding recommended $500,000
- ABSTRACT:
Christian Lorson
Pre-clinical development of E1-targeting ASOs in SMA
Spinal muscular atrophy (SMA) is an autosomal recessive disorder that is the leading genetic cause of infantile death. The gene responsible for SMA is called survival motor neuron-1 (SMN1). SMN2 is nearly identical to SMN1, however, mutations in SMN2 have no clinical consequence. The reason why SMN2 cannot prevent disease development in the absence of SMN1 is that the majority of SMN2-derived transcripts are alternatively spliced, resulting in a truncated and unstable protein.
In this project, we will build upon our previous “basic” molecular biology findings that identified “Element 1” (E1) as a potent repressor of SMN2 exon 7 inclusion. We have generated a lead-candidate antisense oligonucleotide (ASO) that significantly extends survival of two important animal models of disease. In Aim 1, SMN2 splicing will be targeted by our lead candidate E1 ASO in combination with previously described ASOs that target alternative mechanisms leading to SMN2 exon 7 inclusion: ISS-N1 and the intron7/exon 8 junction. In Aim 2, we will examine the co-administration of the E1 ASO with compounds that effectively increase/stabilize the SMN mRNA as a means to increase the intracellular pool of the E1 ASO target. In Aim 3, we move the ASO closer to the clinic by examining efficacy and distribution in a swine model of SMA. We believe an E1 ASO Morpholino will be an exciting and valuable addition to the SMA portfolio.
April 14-15, 2016
OPEN – CONSENT–8-1 REVISED