Adeno-Associated Vector Mediated SOD1 Gene Silencing Therapy in Naturally Occurring Canine Degenerative Myelopathy

Status: Enrollment on brief hold

Description:

Canine degenerative myelopathy (DM) is an inherited, progressive spinal cord disease, generally noticed after the age of 8 years.  Clinical signs are initially very mild and refer to a thoracolumbar spinal cord disease. Over time the clinical signs progress to lower motor neuron signs in the pelvic limbs, paraplegia, and later loss of motor function including in front legs with brainstem signs in the end stage.  Breed and also owner decision are important factors for survival since many dogs are euthanized when they can no longer walk.   The suspected diagnosis of degenerative myelopathy is established by exclusion of disorders causing similar signs such as chronic disk disease, spinal tumors , degenerative lumbosacral stenosis, hip dysplasia, chronic cruciate ligament disease or neuromuscular disorders.   Effective treatment options are not available.

Many cases of canine degenerative myelopathy are caused by mutations in the gene encoding superoxide dismutase (SOD1). The purpose of the study is to determine whether a suppression of the activity of the mutant SOD1 gene can stop the progression of the clinical signs. In this study, the gene suppressing compound, is delivered to the spinal cord and brain using a small vector (known as adeno-associated vector or AAVrh10).

Inclusion Criteria:

  1. Species: canine
  2. Sex: male, castrated male, female , spayed female
  3. Age Range: > 8 years
  4. Weight Range: > 20 kg
  5. Other:
  • History of chronic progressive hind end weakness
  • Ambulatory condition, neurological signs referring to a T3 – L3 localization
  • Only dogs without structural spinal cord lesions such as compressive intervertebral disk disease, spinal tumors, infectious or non-infectious meningomyelitis, malformations and degenerative lumbosacral stenosis will be included.
  • The parameters should be within normal limits for CBC, chemistry profile, chest radiographs and MRI T3 – S1.
  • Only dogs without structural spinal cord disease and a homozygous SOD1 mutation will be enrolled into this study.
  • Signed consent form by owner including that dogs after adeno-associated vector treatment will undergo an autopsy with cremation of the body.

Exclusion Criteria:

  1.  Dogs with structural spinal cord disease such as such as compressive intervertebral disk disease, spinal tumors, infectious or non-infectious meningomyelitis, malformations and degenerative lumbosacral stenosis will be excluded
  2. Dogs with active hepatitis will be excluded
  3. Dogs who are not homozygous for the SOD1 mutation will be excluded
  4.  We will exclude dogs for whom the owner does not sign a consent form.

Client Benefits:

The study will cover all the expenses related to the study and follow-up . This includes additional anesthesia procedures, additional MRI exam to inject the gene suppression compound, CSF analysis, vector treatment, recheck exams, force plate analysis, whole body EMG, motor test conduction of nerves, bloodwork, autopsy and cremation. The initial expenses such as initial neurological examination and intial MRI and anesthesia will not be covered by the study funds. Your pet’s participation will also allow us to gain information which will help in the diagnosis and management and treatment of other dogs diagnosed with degenerative myelopathy, a disorder which is currently not treatable. You understand that your animal’s participation in this study may not alleviate or cure his/her ailment.

Contact information:

For questions regarding the clinical trial please email the clinical trials technician, Diane Welsh at: clinicaltrials@tufts.edu