PREVIOUS DM RESEARCH
SPECIAL GSD DM RESEARCH 2023
German Shepherd Parents... U.S. Followers -WE NEED YOUR HELP!!
We are happy to announce a new up and coming DM research study pertaining specifically to the German Shepherd Dog. {GSD}
We are asking for DNA SAMPLES!
This is a colossal advancement in recent studies, as well as a huge collaborative effort including many different organizations.
Some of those associated with this project include of the following: The German Shepherd Club of America - Carolyn Z. Gerganoff, Health and Genetics Chair. AKC Canine Health Foundation (CHF) - Andrea Fiumefreddo, Director of Programs and Operations. The Broad Institute - Professor Kerstin Linblad-Toh, Scientific Director of Vertebrate Genome Biology. University of Missouri - Joan Coates, Professor of Neurology and Gary Johnson, Associate Professor Dept. of Pathobiolgy.
In short, the objective will be to determine the potential of additional or different genetic factors where it concerns the GSD, even beyond the SOD1 gene mutation reputed to contribute to DM symptoms in other breeds. We have been asked to help provide DNA samples in advance of this project in preparedness.
We do hope you will find it in your heart, for you and your pup to help research for a cure for this disease.
Thank you in advance for your support and consideration of this project.
REQUIREMENTS:
● All GSD symptomatic dogs, and healthy GSD’s dogs that are 7 years or older.
● It would be preferable that you have a presumptive diagnosis of DM to qualify, but
not necessary to apply.
● US Residents only (due to shipping time constraints)
INFORMATION ABOUT THE INTENDED STUDY U.S. DESCRIBED BELOW:
"Canine degenerative myelopathy (DM) is a naturally occurring progressive adult-onset neurodegenerative disease that is fatal. Performing genome-wide association studies (GWAS) in Pembroke Welsh Corgis (PWC), we identified an association to a SOD1 variant, coding for the E40K amino acid substitution, that occurs in >180 dog breeds. The vast majority of breeds with DM have the same SOD1 mutation. Using PWC with the SOD1 disease allele, we compared early onset cases and elderly healthy dogs that also were homozygous for the DM risk allele. A mutation in SP110 was found to predispose to early onset DM. Given that the frequency of the SOD1 mutation and disease is variable within and across breeds we believe that multiple additional genes may affect at what age the disease starts.
Overall, we have collected >20,000 German shepherd dogs (GSD) dogs and genotyped them for the standard SOD1 mutation.
The disease is frequent and the allele frequency in GSD is 35%. In this proposal we will perform health updates for already collected and novel GSDs and look at the age of onset distribution. We will then select up to 250 old healthy dogs to compare them to the 250 dogs with the earliest onset (both categories having two copies of the SOD1 mutation). This should identify novel modifier genes determining if SOD1+ dogs get the disease early or late (or not at all). Finally, we will perform whole-genome sequencing of three GSDs with the disease, but lacking the known SOD1 mutation, to identify additional risk factors.
IF YOU ARE INTERESTED, PLEASE CLICK THE BELOW LINK, PRINT OUT APPLICATION AND FOLLOW INSTRUCTION.
MAKE A NOTE ON THE FORM: "German Shepherd DM Research Project" on left side of submission form. That way there will be
no charge.
'PROJECT NEW HOPE' RESEARCH UPDATE - 2019 Dec 31
Just a quick update on the research initially sponsored by the 'Finding the Cure for DM Foundation Inc.'. through generous contributions.
Regarding 'Project New Hope' - latest efforts were on the development of an IV form of the therapy to replace the need to inject it intrathecally (into the cerebrospinal fluid) - the test agent was developed and manufactured and clinical testing should be commencing in the new year.
The clinical trial funded by Morris Animal Foundation is ongoing and going well. This trial was made possible by the work performed in 'Project New Hope', initiated and funded by the 'Finding the Cure for DM Foundation Inc.'.
'PROJECT NEW HOPE' UPDATE ON PHASE 2 STUDY- 2019 Aug
"With the generous funding and continued support from the Finding a Cure for DM Foundation, the Phase 2 study of the New Hope project allowed us to make further progress in demonstrating the use of the U1 Adaptor Oligonucleotide (U1AO) gene silencing technology for the therapeutic application to DM. The U1AO design is notable for its efficiency in uptake, potency, and specific and long-lasting target effect, without any induction of immune response and it represents an ideal candidate for DM.
The aim of the study was to show that a U1AO formulation able to silence canine SOD1, called U1cSOD1, administered intrathecally (into the CSF) to both normal and end stage DM-affected dogs would be well-tolerated with no adverse effects and would achieve silencing of the canine SOD1 gene. We have demonstrated that U1cSOD1 achieves therapeutically relevant SOD1 gene-silencing in dogs with and without DM. Our work has allowed to conclude the following:
• Treatment with U1cSOD1 does not cause any side effects in dogs.
• U1cSOD1 does silence the mutated SOD1 gene in dogs.
This work resulted in the identification of U1cSOD1 as a promising treatment for DM due to the following successful results:
• U1cSOD1 maintains its high efficacy and stability in dogs.
• U1cSOD1 is safe in dogs.
• U1cSOD1 effectively silences expression of the SOD1 gene in dogs with DM.
Thanks to this phase of work funded by the 'Finding a Cure for DM Foundation' we were able to obtain a grant from the Morris Animal Foundation to treat dogs with DM. In this clinical trial we are evaluating the safety and clinical effects of monthly U1cSOD1 treatment in DM dogs. We are glad to report that the Morris study is going very well and that we now feel very confident about the safety of our therapy.
In view of this and to gather data that would be required to fund an extensive DM clinical trial, which is our long-term goal, we have initiated work to look at the route, dose and dosing frequency needed to achieve the best results by measuring levels of U1cSOD1 and SOD1 in the blood, urine and CSF of dogs undergoing treatment. The ultimate goal is to find the efficacious dose and dosing frequency with the least invasive delivery method for the dogs to minimize the number of treatments needed.
2018 Dec 10: MORRIS ANIMAL FOUNDATION AWARDS GRANT!
The Finding the Cure for DM Foundation ARE PLEASED AND EXTREMELY GRATEFUL TO ANNOUNCE that the MORRIS ANIMAL FOUNDATION has awarded our 'PROJECT NEW HOPE' research team a grant to continue research along the same lines as our own sponsored study!!!
This is exciting news for the potential beneficial treatment for our DM pups!
We are immensely thankful and for each and every one of you that have and continue to support FCDMF in our quest to help our DM pups and families.
It is with data that was collected through Project New Hope that you supported and sponsored, that our team was able to be awarded this grant. We are hopeful of a very positive outcome as a result!
“The scope of this grant is to investigate the safety of the U1 Adaptor technology in dogs with DM. In this safety trial in 4 dogs diagnosed with degenerative myelopathy, we will deliver a U1 Adaptor-technology-based treatment that silences the SOD1 gene into the cerebrospinal fluid around the spinal cord to prevent production of SOD1 protein within neurons. The treatments will be repeated every month up to 12 months, perhaps even longer, and the treated dogs will be monitored for side effects and for a change in progression of their clinical signs. Demonstration of safety of this treatment will allow us to perform a much larger clinical trial to determine whether U1 Adaptor targeting of SOD1 is an effective treatment for a disease that is currently fatal.”
UPDATE ON PHASE TWO OF 'PROJECT NEW HOPE!'
- STAGE ONE! 2018 Jan 24
The Finding the Cure for DM Foundation are very pleased to provide an update on Phase Two, stage
one (of 3) of Project "New Hope". We are very optimistic and remain very hopeful for more positive
outcome in the future! We could never have gotten this far without your support. We are very thankful
to you all for your generous donations and continued support!
Here is an update, as provided by the doctors involved in this research:
"Dear friends, We would like to update you on our New Hope Phase 2
project. We are very happy to report that the first stage of the study is complete with very exciting
preliminary results. The first dogs were treated achieving good gene silencing and no adverse
conditions! The initial expectations were successfully met and we hope for further great results. Thanks to your support, we are now able to start the second phase in which we will confirm our preliminary results and we anticipate we will have enough data to design our first clinical trial for dogs with DM. As you know this study is very important as it will establish a foundation towards a therapy for DM.
Thank you again for your support and we look forward to providing an update at the end of this work."
Drs. Natasha Olby and Sam Gunderson.
FCDMF has been sponsoring project "New Hope", a new, initial research project with the ultimate goal of silencing the gene(s) that contribute to DM symptoms. If successful, we anticipate it will stop further progression of symptoms in its tracks.
Currently, the ONLY funding has been by your donations through Finding the Cure for DM Foundation. We hope you will find it in your heart to continue your generosity, bringing us one step closer to a Cure! Thank you for all you have done to help us initiate this promising research!
2016 UPDATE- Apr 29
2016 April 29: While the initiation of Project New Hope was aimed at evaluating the possibility of silencing the SOD1 gene, which by many is perceived to be a contributing factor to DM, we have now evaluated a different gene.
Due to the positive preliminary progress report for silencing the cSOD1 gene, we have now extended this study to include another gene reputed to have some significance in DM symptoms. The Canine DRB1 gene, also reputed to contribute to the symptoms of Degenerative Myelopathy. WE HAVE VERY POSITIVE RESULTS! Our science team at Silagene has concluded that in vitro, using their U1 Adaptor technology, they have indeed been able to silence the Canine DRB1 gene! This is terrific news, and is a direct reflection of our supporters pulling together for a great cause, so close to all of our hearts! Thank you..one and all, for believing in and continuing to help support this research! However, it does not end here. Project "New Hope" is only in it's infancy stage. We will now be taking steps into finding a Clinical Veterinarian to participate and continue reaching further into this study, in the hopes of eventually leading us into Canine Clinical Trials!
Contrary to the ALS comparison, investigating DRB1 has led scientists to believe that GSDM may be a different “type” of DM, inherently more like PPMS (Primary Progressive MS.)
Targeting this second gene will enhance the ability to bring in DM-expert veterinarians for moving the project forward. Furthermore, being able to target two genes, either alone or together, should greatly broaden the interest to those who want to do clinical trials. Please see the newest update below, and please consider FCDMF for your charitable contributions to continue to help move these studies forward.
FDCMF, through your donations, is currently the ONLY funding source for project New Hope.
We at FCDMF wish to thank all who have contributed to initiate this program, and those who continue to help see it continue.
We are more than grateful to have you fighting DM beside us! Thank You!!
2016 - Feb 13 - ADDENDUM TO 'PROJECT NEW HOPE'
This addendum for the SOD1 silencing consists of the evaluation of the DLA-DRB1 gene that we would like to extend into project "New Hope."
While the initiation of Project New Hope was aimed at evaluating the possibility of silencing the SOD1 gene, which by many is perceived to be a contributing factor to DM, Due to the positive preliminary progress report for silencing the cSOD1 gene, we would like to extend this study to include another gene reputed to have some significance in DM symptoms.
This next portion of the study would revolve around the silencing of the DLA-DRB1 gene. In past studies, related research indicated that DRB1 housed the 1101 allele, also thought to contribute primarily to GSDM. Contrary to the ALS comparison, investigating DRB1 has led scientists to believe that GSDM may be a different “type” of DM, inherently more like PPMS (Primary Progressive MS.)
Targeting a second gene will enhance the ability to bring in DM-expert veterinarians for moving the project forward. Furthermore, being able to target two genes, either alone or together, should greatly broaden the interest to those who want to do clinical trials.
While the initial study into the feasibility of silencing the SOD1 gene has been funded by previous donations and fundraising events, future studies to initiate research and silencing of the DLA-DRB1 gene, will require additional funding.
To date, the ONLY funding of this project has been with your donations through the Finding the Cure for DM Foundation. We hope you will find it in your heart to continue your generous contributions to this much needed research.
We at FCDMF wish to thank all who have contributed to initiate this program, and those who continue to help see it continue.
Please review the attached proposal for the possibility of extending DM research into silencing of the DRB1 gene.
2016: 'PROJECT NEW HOPE' RESEARCH UPDATE!!
We would like to share the preliminary progress of Project New Hope, SOD1 gene silencing. In this initial in vitro study, Silagene has had very good success in silencing up to 75% of the SOD1 gene, with their patented U1 Adaptor Technology.
This is wonderful news, and offers great potential for continuing this line of research!
It is our hope that with continual funding, it may be possible to continue research and be into canine clinical trials of this procedure within a year. The attached document outlines the progress of Project New Hope up to this point in time. We anticipate it will fill your heart with “New Hope,” as it has ours!
Furthermore, due to the positive preliminary results with the SOD1 gene, in a time and money saving opportunity, we would like to move forward with an extension of the current study to another gene reputed to be a possible link to canine DM.
This next portion of the study would revolve around the silencing of the DLA-DRB1 gene, which houses the 1101 allele.
Please anticipate the next announcement which clarifies the purpose of the intended work on the DLA-DRB1 gene.
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