Further success in the treatment of neuromuscular diseases

A clinical study by Great Ormond Street Hospital (GOSH) has shown encouraging results in treating a type of neuromuscular disease known as Brown-Vialetto-Van Laere syndrome (BVVL) with the vitamin riboflavin. 

Neuromuscular disorders such as BVVL cause the breakdown of muscle and nerve tissue. They can occur from birth or develop later in life, and can be either stable or degenerative.  Symptoms range from almost undetectable, to the progressive loss of muscle function, sensory impairment, paralysis and death. 

Patients with BVVL are deficient in riboflavin or vitamin B2, an essential vitamin necessary for normal metabolic function. Patients taking part in the study were given a daily high dose of oral riboflavin in an effort to help some of their symptoms.

Findings from the study, which included 18 children internationally, conclude that high-dose oral riboflavin can be effective in treating this condition and is most beneficial when introduced soon after the onset of symptoms, which include vision and hearing loss, upper limb weakness and respiratory insufficiency.

BVVL, which is an autosomal recessive genetic condition, can be caused by mutations in the SLC52A2 gene, which is responsible for the expression of a riboflavin transporter.  In 14 of the 16 patients who were given high-dose riboflavin, some improvement or stabilising effect was observed.

Professor Francesco Muntoni (Great Ormond Street Hospital and UCL Institute of Child Health) and Professor Henry Houlden (National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology) are senior authors on the study, published in the journal Brain.

This latest success is another example of how momentum in this area is building. Professor Muntoni’s team have identified over 20 disease-causing genes and are leading clinical trials of new therapies – especially in Duchenne muscular dystrophy. These range from highly innovative first-in-man studies of new treatments, to vitamin replacement therapies such as this.

Professor Francesco Muntoni said: “In the last five years, we’ve had successes in understanding which genes give rise to neuromuscular diseases, what these genes do and how we can harness this knowledge to improve the lives of children. These latest findings are another example of how our increasing understanding of the genetic bases of these diseases can inform therapeutic developments to combat them.”

Case study 

Twelve-year-old Demi from Newcastle was diagnosed with BVVL at GOSH in 2011 and has been taking daily high-dose riboflavin for over two years. Her mother Tracey explains:

“Demi can sit and stand independently for the first time in three years. The mobility in her hands is so much better. She has put on weight, grown in height and shoe size and her hair has grown, all of which had remained the same between the age of 6 and 10.”

“It’s amazing to think that such a simple intervention could have such a profound effect. Having struggled for so many years to get a diagnosis for Demi, it was very hard to stay positive and it was difficult to imagine any good news. Life is still very challenging for Demi, but this clinical study has helped her significantly.”

“Doctors at GOSH have been absolutely amazing in helping and supporting us, Demi is finally on medication which is proving to have a positive effect on her.”

Professor Francesco Muntoni, Director of the GOSH/ICH Dubowitz Neuromuscular Centre, and MRC Centre for Neuromuscular Disorders, said: “These observations show that there is a simple and effective intervention that can become part of the child’s daily routine at home. There are no reported side effects and clearly we’re very encouraged by the results we’ve seen to date from this study.”