Degenerative Myelopathy of the German Shepherd Dog (GSDM)

Report Date: April 15, 2007:

This past year has been exciting and productive. We uncovered specific changes in DNA of dogs with GSDM (based upon ante-mortem diagnostics). First, there is a priming error in region DLA-DRB1 associated with a point change in allele*1101, the DM Flash test. This is a new allele*1101J. The location of allele*1101J is where DNA encodes T cell recognition of antigens and predispose for auto-immune diseases. There is a 70 BP deletion in the DNA region that encodes folding of myelin basic protein and is thought to result in increased antigenicity of MBP in Finish MS patients. Most GSDM dogs have changes in 2 regions associated with primary progressive MS, confirming that GSDM is PPMS. The region associated with exacerbating/remitting MS is normal. We have also evaluated new medications. PEG, which is effective in treating acute spinal cord disease, has minimal effectiveness on initial dosing only. Stem cell therapy with intrathecal (but not intravenous) bone marrow-derived progenitor cells improves motor function and spinal conduction for a short time. Stem cell therapy can be safely done and repeatedly, but may not be the final answer. We are evaluating whether the nerve growth factors that these cells produce are what is needed and whether a more long-term delivery system for these factors can be found. Trials with drugs which help human PPMS patients have begun to see if they will help GSDM patients. So, we are close to understanding what GSDM is and to developing new strategies for its treatment.

The DM Flash Test has allowed for testing of normal and affected dogs and there is a high probability of affected dogs to carry several characteristic loci in their genomes. In this study, we will determine the incidences of GSDM-related genes in a large number of GSDs and evaluate the clinical significance of these findings. In a small pilot study, approximately 20% of GSDs carry the potential to develop GSDM. This study will expand upon these findings and confirm the data rom the smaller sample. We will also attempt to determine if there are geographic congregations of such genetics in this country. This study will help us to identify relative risk of GSDM in the GSD. We hope that the study will allow us to identify individuals at risk so that we can try to modify their potential to develop GSDM in the future.

Report Date: May 24, 2005:

Dr. Clemmons has, today, completed the first autologous bone marrow-derived stem cell transplant in a dog with German Shepherd DM. Dr. Clemmons and his team are cautiously optimistic that it will help but it is too early to determine that. He will be monitoring this dog over the next month to see if there are improvements in neural function. What we know so far, is that it has not appeared to have any adverse effects in the first 12 hours after transplantation. The dog has shown no fever, is happy and hungry.

Report Date: December 4, 2004:

We are now able to accept samples for DNA evaluation, at least in suspect affected GSDM dogs. We can run the test for people, knowing that it may be negative in a number suspect cases. However, we cannot run it for free since the reagent cost is currently high. We are asking people to make a donation to the University of Florida Foundation with “for Dr. Clemmons’ research” in the memo section and send the check along with a CBC sample on a cold pack to us overnight delivery. The local veterinarian may be able to help you with this. We will provide the results within 2 weeks. We still feel it should not be the sole diagnostic run for the disease, but it may go a long way toward confirming the presence of GSDM. In the future we may be able to reduce the cost by using our Fed Ex number, but this is a start.

Thirdly, we are hoping that we will be able to start stem cell transplantation of bone marrow-derived mesenchymal stem cells early next year. There are several cases with whom we are talking. Our hope is that the stem cells will fix the dogs and necropsies will be a long time off.

We can’t help everyone and we will have to be fairly selective on the imaging and stem cell studies for the moment, but the floodgates are open for sampling DNA. If we can eventually control the costs (by Volume) we might be able to use any remainder of money to help defray the costs for the stem cells.