VBP-15 for Duchenne Muscular Dystrophy

Prednisone has been used since the 1970s for delaying the otherwise obligatory progressive motor deterioration seen in  Duchenne Muscular Dystrophy (DMD.

A good deal of data has been acquired over the years.  In fact there are even ongoing studies looking at different dosing regimens.

The drug is typically started between ages 4-6 at a dose of 0.75 mg/Kg.  However, steroid cause may side effects to Duchenne boys, including weight gain and behavioral problems.

How does it work?  We’re not sure, but we think the medication stabilizes muscle membranes and inhibiting cytotoxic T-cells.

Side effects are mediated by binding sites in the cell nucleus which lead to initiation of metabolic pathways :
NM2

The new drug VBP-15 is molecularity very similar to Prednisone, but lacks the 11 beta hydroxy arm, which reduces the metabolic side effects, without affecting the beneficial membrane stabilizing effects:

nm3

VBP-15 has been shown to improve muscle strength and function in an animal model of DMD without the metabolic side effects of Prednisone:

nm4

Clinical trials in humans are expected to begin in 2013-14.

Watch this space for more information.

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New study compares steroid regimens in boys with Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) affects 1 in 3,600 boys and is caused by a mutation in the dystrophin gene, resulting in progressive muscle weakness.

Affected male children are normal at birth, but develop signs of muscle weakness before age 6, usually first affecting the legs and pelvis, causing difficulty getting up from the floor or a sitting position, and difficulty climbing stairs. Untreated boys are usually wheelchair dependent by age 12.

Ongoing research is leading towards pre-symptomatic diagnosis of DMD, and there has been some progress in genetic therapy for affected boys identified in these early stages of the disease.

However, so far corticosteroid therapy is the only treatment that has been shown to increase muscle strength in boys already affected with symptoms of DMD.

Steroids can cause side effects, and there is wide variability whether doctors doctors prescribe prednisone or deflazacort, as well as the dosing, duration of steroid use or even whether steroids are prescribed at all.

A new study aims to answer some of these questions.

The study is looking to enroll boys aged 4-7 with genetically confirmed DMD who have not taken steroids before.

They will be included in the study for 3-5 years and receive either:
1. Prednisone 0.75mg/Kg/d, or
2. Prednisone 0.75mg/Kg/d 10days on then 10 days off, or
3. Deflazacort 0.9mg/Kg/d

They will need hospital visits every 3 months for the first 6 months, then every 6 months thereafter.

This study is available locally at Penn Sate Hershey Medical Center – parents or physicians of interested patients should contact Beth Stephens at 717-531 0003 extension 283395 or by email for more information.