Our drug-repurposing clinical trial of dantrolene sodium in patients with Wolfram syndrome has been almost concluded. Nineteen patients could successfully complete the required six-month phase, and many of them decided to stay on dantrolene sodium another 18 months. The results of this open-label clinical trial (all the participants took dantrolene sodium) show that dantrolene sodium is well tolerated by patients with Wolfram syndrome. Although the study was small, a select few patients seemed to have improvements in diabetes-related outcomes, which might correlate with a positive trend in other outcome measures, including visual acuity and brain functions. This study justifies further investigation into using dantrolene sodium and other new drugs targeting the same molecular pathway for the treatment of Wolfram syndrome.
Depression and the link between cardiovascular disease in patients with type 2 diabetes.
https://www.sciencedirect.com/science/article/pii/S1056872720304785
To further improve the clinical care for patients with Wolfram syndrome and Wolfram-related disorders, I have created a new genetics clinic at Center for Advanced Medicine, Washington University Medical Center. We offer genetic evaluations, education, and counseling for patients and family members of all ages with or suspected to have Wolfram syndrome or WFS1-related
disorders. We also provide personalized management plans based on the type of your gene variants together with other specialists at our medical center, such as Dr. Marshall, Dr. White, Dr. Hoekel, and beyond. To make an appointment with me, please call 314-747-7300 or 314-747-3294 (if you are participating in our research clinic/registry or interested in participating in the research). You can also send an email to WolframSyndrome@wustl.edu.
We could cover the costs for genetic testing if your insurance does not cover the entire amount of the costs.
Our team’s goal is to discover, test and develop treatments in order to prevent or limit visual impairment and to improve the autonomy and the quality of life of patients with Wolfram syndrome.
Update March 5, 2024:
Recently we have identified a family of molecules with the capacity to significantly stimulate the growth of retinal ganglion cells in vitro in a model of optic atrophy. We developed a zebrafish model with an optic atrophy and we have treated these fishes with one of these molecules. We used increasing doses of molecules to measure the toxicity and determine the most effective dose to protect the optic nerve. We have determined the dose with the best effect and confirmed that treatment with this molecule can prevent optic nerve developmental delay in vivo in our model of optic neuropathy. We are studying the mechanism of action of this molecule and using it in several model of Wolfram syndrome. We look forward to a clear indication of the possibility of using this molecule in the future development of a treatment for Wolfram syndrome.
Gene therapy projects using WFS1 are also important for us. We have synthesized a novel AAV2/9-WFS1 vector to treat all affected tissues in a previously established mouse model of Wolfram syndrome. After injection of the vector in young mice, we have checked that the vector could transduce all affected tissues including, eye, ear, brain and pancreas. We are now evaluating the efficacy of this gene transfer on the visual and auditory function of our mouse model.
Update May 26, 2023:
Development of a novel molecule to treat optic atrophy in Wolfram syndrome
Wolfram syndrome is a devastating multisystemic disorder and despite decades of intense research, no curative therapies are currently available. All aspects of this disease reinforce our commitment to elaborate a therapeutic strategy for Wolfram patients.
We have identified a molecule with the capacity to stimulate significantly the growth of retinal ganglion cells in vitro in a model of optic atrophy. This molecule appears to represent interesting therapeutic candidate for the disease. We have generated a zebrafish model reproducing an optic atrophy similar to that observed in wolfram syndrome. In this model we show a decrease of optic nerve volume and retinal ganglion cell number, and a decrease of visual motor response. To obtain information on whether our molecule could be used in the future development of a treatment for Wolfram syndrome we have treated our optic atrophy zebrafish model. Very interestingly our preliminary results show a significant protection of the optic nerve from degeneration in early stage in the treated model. Our project is now to study the mechanism of action of this molecule and use it in several model of Wolfram syndrome. These results can raise the interesting possibility of a future therapy.
Update October 9, 2020:
For the last 20 years, our group together with Pr Christian Hamel has made highly significant contributions concerning the clinics, genetics and pathophysiology of autosomal inherited optic neuropathies, by identifying the genes involved in these diseases, analyzing mouse models reproducing human pathologic mutations, deciphering the basic function of the uncharacterized genes and start therapy projects in this field.
Wolfram syndrome is a devastating multisystemic disorder and despite decades of intense research, no curative therapies are currently available. All aspects of this disease reinforce our commitment to elaborate a therapeutic strategy for Wolfram patients.
Our team are working on two axes:
- Development and testing of new therapeutic drugs
- Use gene therapy delivering WFS1 to treat Wolfram syndrome
Recently we have identified a family of molecules with the capacity to stimulate significantly the growth of retinal ganglion cells in vitro in a model of optic atrophy. These molecules appear to represent interesting therapeutic candidates for the disease. Our project is to test the efficacy of these molecules in a previously established mouse model of Wolfram syndrome.
Gene therapy has exciting potential. For several reasons, gene therapy will have considerable therapeutic potential in this monogenic disorder. In our first gene therapy
studies in a mouse model of Wolfram syndrome, we have demonstrated that it is possible to rescue visual function using overexpression of WFS1 when it is administrated into the
vitreous. To go further, we hypothesized that a systemic delivery of WFS1 could restore WFS1 expression and function in both retinal ganglion cells and other organs. Our project will evaluate functional evidence that WFS1 expression by systemic gene transfer in a Wolfram model greatly mitigates the development of the phenotype.
Our projects represent a first step in acquiring the proof of principle necessary for carrying out clinical trial in human. Our link with the reference center for genetic sensory diseases Maolya in Montpellier will help us to improve preclinical to clinical translation.
Cécile Delettre
Neuropathies Optiques Héréditaires et Déficits Mitochondriaux
Inherited Optic Neuropathies and Mitochondrial Disorders
INSERM U 1051 – Pathologies sensorielles, Neuroplasticité et Thérapies
Institut des Neurosciences de Montpellier
Hôpital Saint Eloi, 80 rue Augustin Fliche
BP74103, 34091 MONTPELLIER Cedex 5
Tel: (33/0) 499 63 60 30 Fax: (33/0) 499 63 60 20
Oct 8, 2020:
The negative phycological impacts of diabetes stigma.
https://care.diabetesjournals.org/content/early/2020/09/02/dc19-2447.abstract
October 6, 2020:
A new manifestation of neovascularization in a study with mice.
About the Snow Foundation
The Snow Foundation is a collective voice for Wolfram syndrome patients, working towards a cure for Wolfram syndrome and developing novel therapies for diabetes, vision loss, hearing loss and neurodegeneration.
Rare Diseases…Common Problems
P.O. Box 50224 Clayton, MO 63105
(402) 694-1354