Jean-Laurent Thibaud

Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs.

Duchenne muscular dystrophy remains an untreatable genetic disease that severely limits motility and life expectancy in affected children. The only animal model specifically reproducing the alterations in the dystrophin gene and the full spectrum of human pathology is the golden retriever dog model. Affected animals present a single mutation in intron 6, resulting in complete absence of the dystrophin protein, and early and severe muscle degeneration with nearly complete loss of motility and walking ability. Death usually occurs at about 1 year of age as a result of failure of respiratory muscles. Here we report that intra-arterial delivery of wild-type canine mesoangioblasts (vessel-associated stem cells) results in an extensive recovery of dystrophin expression, normal muscle morphology and function (confirmed by measurement of contraction force on single fibres). The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients.

Successful treatment of cervical spinal epidural empyema secondary to grass awn migration in a cat

Spinal epidural empyema (SEE) represents a severe pyogenic infection of the epidural space. Clinical signs of the disease are non-specific – increased body temperature, intense neck pain, neurological signs of a transverse myelopathy – and can lead to severe and permanent neurological deficits. This report describes the diagnosis and successful surgical treatment of cervical SEE secondary to grass awn migration in a cat. Although it is uncommon, this disease should be suspected in cats with progressive myelopathy. Early diagnosis and emergency surgery combined with antibiotic therapy are required to allow a complete recovery.

Splitting of Pi and other 31P NMR anomalies of skeletal muscle metabolites in canine muscular dystrophy

Many anomalies exist in the resting 31P muscle spectra of boys with Duchenne muscular dystrophy (DMD) but few have been reported in Golden Retriever muscular dystrophy (GRMD), the closest existing animal model for DMD. Because GRMD is recommended for preclinical evaluation of therapies and quantitative outcome measures are needed, we investigated anomalies of 31P NMRS in tibial cranial and biceps femoris muscles from 14 GRMD compared to 9 control (CONT) dogs.

Effects of an Immunosuppressive Treatment in the GRMD Dog Model of Duchenne Muscular Dystrophy

The GRMD (Golden retriever muscular dystrophy) dog has been widely used in pre-clinical trials targeting DMD (Duchenne muscular dystrophy), using in many cases a concurrent immune-suppressive treatment. The aim of this study is to assess if such a treatment could have an effect on the disease course of these animals. Seven GRMD dogs were treated with an association of cyclosporine A (immunosuppressive dosage) and prednisolone (2 mg/kg/d) during 7 months, from 2 to 9 months of age. A multi-parametric evaluation was performed during this period which allowed us to demonstrate that this treatment had several significant effects on the disease progression. The gait quality as assessed by 3D-accelerometry was dramatically improved. This was consistent with the evolution of other parameters towards a significant improvement, such as the clinical motor score, the post-tetanic relaxation and the serum CK levels. In contrast the isometric force measurement as well as the histological evaluation argued in favor of a more severe disease progression. In view of the disease modifying effects which have been observed in this study it should be concluded that immunosuppressive treatments should be used with caution when carrying out pre-clinical studies in this canine model of DMD. They also highlight the importance of using a large range of multi-parametric evaluation tools to reliably draw any conclusion from trials involving dystrophin-deficient dogs, which reproduce the complexity of the human disease.

Progressive Myelopathy Due to a Spontaneous Intramedullary Hematoma in a Dog: Pre- and Postoperative Clinical and Magnetic Resonance Imaging Follow-up

A 4-year-old, male Jack Russell terrier was presented for a 6-month history of progressive right hemiparesis with episodic cervical hyperesthesia. The neurological examination showed a right-sided, upper motoneuron syndrome and partial Horners syndrome. Two magnetic resonance imaging (MRI) examinations were performed 3 months apart and revealed a persistent cervical intramedullary hematoma. A dorsal myelotomy was performed. A subacute hematoma was confirmed histologically without underlying lesions. Eighteen months later, the dogs clinical signs were minimal. Two MRI examinations were performed 2 weeks and 5 months after surgery and revealed regressing signal abnormalities at the surgical site, consistent with a surgical scar.

Juvenile-onset polyneuropathy in American Staffordshire Terriers

Background The only hereditary neurologic disorder described so far in American Staffordshire Terriers is adult‐onset cerebellar degeneration secondary to ceroid lipofuscinosis. We have seen several dogs with a newly recognized neurological disease characterized by locomotor weakness with or without respiratory signs and juvenile onset consistent with degenerative polyneuropathy of genetic origin. Objectives To characterize a novel polyneuropathy in juvenile American Staffordshire Terriers. Animals Fourteen American Staffordshire Terriers presented with clinical signs consistent with juvenile‐onset polyneuropathy at 5 veterinary hospitals between May 2005 and July 2017. Methods Case series. Dogs were included retrospectively after a diagnosis of degenerative polyneuropathy had been confirmed by nerve biopsy. Clinical, pathological, electrophysiological, histological data, and outcome were reviewed and a pedigree analysis performed. Results All dogs displayed clinical signs of neuromuscular disease with generalized motor and sensory involvement, associated with focal signs of laryngeal paralysis (10/14 dogs) and megaesophagus (1/14 dogs). Histopathological findings were consistent with degenerative polyneuropathy. Follow‐up was available for 11 dogs, and 3 dogs were euthanized shortly after diagnosis. In these 11 dogs, the disease was slowly progressive and the animals maintained good quality of life with ability to walk. Pedigree analysis was mostly consistent with an autosomal recessive mode of inheritance. Conclusions and Clinical Importance Juvenile polyneuropathy, associated with laryngeal paralysis, is a newly described entity in American Staffordshire Terriers, and results from degenerative neuropathy. When surgery for laryngeal paralysis is performed, lifespan may be similar to that of normal dogs even though affected dogs have locomotor disturbance.