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Victor Dubowitz

Publications and source records attributed to Victor Dubowitz.

9 recordsLinked to original sources
PubMed2004

Therapeutic efforts in Duchenne muscular dystrophy; the need for a common language between basic scientists and clinicians.

Major advances in molecular genetics of Duchenne dystrophy over the past decade have generated a flurry of attempts at potential cell and gene therapy, mainly in the dystrophin-deficient mdx mouse. This has been accompanied by a fanfare of publicity, in both scientific and lay press, producing waves of hope followed by troughs of disappointment and frustration in both patients and their families and in the scientific community. It has also spawned an additional problem in the use of inappropriate terminology to describe clinical or pathological changes in experimental animal studies, which have been equated with the human disease. It seemed timely to address and hopefully redress the problem, and suggest some solutions, aimed at finding a common language for basic and clinical scientists in their therapeutic efforts in relation to Duchenne dystrophy. Core problems include equating the mdx mouse, with its very mild clinical phenotype, and Duchenne dystrophy; use of inappropriate and often emotive terminology to describe pathological changes, such as 'rescue', 'reversal', 'prevention', 'phenotype', instead of clear descriptive language; and use of the term therapy in place of experiment in both laboratory and clinical experiments targeting single muscles. A major missing link in these multidisciplinary efforts is the absence of mouse clinicians, who can define at a clinical level the motor, respiratory and cardiac deficits in the dystrophic animal, and bridge the huge gap between the mouse scientists doing experimental studies in the laboratory and the clinicians and veterinarians caring for humans and dogs with these disorders.

Animals↗
PubMed2004

Current and future therapy in muscular dystrophy; need for a common language between basic scientists and clinicians.

This paper reviews the current therapy of Duchenne dystrophy, with the only two effective means of prolonging ambulation being the provision of knee-ankle-foot orthoses, and administration of corticosteroids, and the prospects, for the future application in Duchenne dystrophy, of ongoing research in cell therapy, gene therapy, protein upregulation and pharmacological possibilities. A critical review is also provided on the inappropriate nomenclature currently used and the need for a common language between basic and clinical scientists. Amongst the major problems are equating the mdx mouse, with its mild clinical phenotype, and Duchenne dystrophy, with its clearly defined severe clinical phenotype; the use of inappropriate and often emotive terminology to describe the pathological changes, such as "rescue", "reversal", "prevention", in place of describing the actual changes in acceptable descriptive language; and the use of the term therapy, in place of experiments, both in the basic laboratory studies and also the clinical experiments of injection of cells or gene constructs into single small muscles. A missing link in the multidisciplinary efforts, in this field, is the almost total absence of mouse doctors, who can define, at a clinical level, the motor, respiratory and cardiac deficits in the dystrophic animal, and bridge the gap between the mouse scientists doing experimental studies in the laboratory and the clinicians and veterinarians involved in the care of humans and dogs with these disorders and speaking the same language in relation to the clinical aspects and the pathology.

Adrenal Cortex Hormones↗
PubMed2003

Phenotypic spectrum associated with mutations in the fukutin-related protein gene.

We describe 22 patients with mutations in the fukutin-related protein (FKPR) gene. Four patients had congenital muscular dystrophy (MDC1C), with presentation at birth, severe weakness and inability to stand unsupported. The other 18 had limb girdle muscular dystrophy (LGMD2I). Eleven showed a Duchenne-like course with loss of ambulation in the early teens while 7 had a milder phenotype. Muscle biopsy invariably showed abnormal expression of a-dystroglycan. MDC1C patients either carried 2 missense or 1 missense and 1 nonsense mutations. Patients with LGMD2I shared a common mutation (C826A,Leu276Ileu) and their phenotypic severity was correlated with the second allelic mutation.

Adolescent↗
PubMed2003

Large in-frame deletions of the rod-shaped domain of the dystrophin gene resulting in severe phenotype.

BACKGROUND: The prediction that Duchenne muscular dystrophy patients have out-of-frame deletions and Becker muscular dystrophy patients have in-frame deletions of the dystrophin gene holds well in the vast majority of cases. Large in-frame deletions involving the rod domain only have usually been associated with mild (BMD) phenotype. OBJECTIVES: To describe unusual cases with large in-frame deletions of the rod-shaped domain of the dystrophin gene associated with severe (Duchenne) clinical phenotype METHODS: Screening for dystrophin gene deletion was performed on genomic DNA by using multiplex polymerase chain reaction. Needle muscle biopsies from the quadriceps were obtained using a Bergström needle. The biopsies were stained with histologic and histochemical techniques as well as monoclonal antibodies to dystrophin 1, 2 and 3. RESULTS: In three children with large in-frame deletions of the rod domain (exons 10-44, 13-40 and 3-41), early-onset weakness and a disease course suggested the DMD phenotype. CONCLUSIONS: This observation emphasizes the uncertainty in predicting the Becker phenotype in a young patient based on laboratory evaluation, and that the clinical picture should always be considered.

Dystrophin↗
PubMed2002

An effective, low-dosage, intermittent schedule of prednisolone in the long-term treatment of early cases of Duchenne dystrophy.

The aim of this study was to evaluate the long-term effects in young children with Duchenne dystrophy of an intermittent low dosage regime of prednisolone (0.75 mg/kg per day for 10 days per month, or 10 days on and 10 days off). Six children under 5 years with Duchenne dystrophy have been commenced on this schedule, four of whom have been followed for at least 30 months and are reported here. All four presented with classical Duchenne dystrophy, and had an out-of-frame deletion in the Duchenne gene and absence of dystrophin in their muscle. All four showed a rapid and dramatic response in muscle function and strength. In three of the four there was an almost complete remission of all clinical signs of dystrophy. Their functional scores remained well above the average scores recorded in untreated Duchenne boys at the same age. There was no increase in weight, stunting of growth, decreased bone density or any other significant side effects related to the prednisolone. Our current experience suggests that this intermittent, low-dosage prednisolone regime is well tolerated and can be safely given long-term in young children with Duchenne dystrophy. The striking response also suggests that there may be an optimal window for treatment of Duchenne dystrophy in the early stages of the disease.

Body Weight↗