Ullrich congenital muscular dystrophy (UCMD) is caused by a change in one of the three collagen VI genes (which are called COL6A1, COL6A2 and COL6A3). This results in very little or no collagen VI protein being produced in the body. This means a vital protein that acts as a scaffold supporting muscle cells is missing. It causes muscles to weaken and waste over time, leading to increasing disability.
Children with Ullrich CMD have weak muscles, are often double jointed in their hands and feet and have stiffness in the spine and joints such as the elbows or hips. Breathing problems tend to develop which require ventilator support. Research indicates 50% of children with Ullrich CMD are full-time wheelchair users by age 11; even for those classed as ‘intermediates’ on the Collagen IV spectrum, 50% have gone off their feet by the age of 21.
Children with Ullrich CMD develop ‘contractures’, this means that the muscle tendons tighten up and the limbs and joints cannot be moved freely. Most of the children with Ullrich congenital muscular dystrophy also develop a curvature of the spine (scoliosis). Another frequent problem after the first few years is weight loss (failure to thrive) which requires nutritional supplementation. As collagen VI is also normally present in the skin, children may have a tendency for scars to heal slowly or become thickened and elevated (keloid formation).
Hope for a cure
Thanks to funding for the Ullrich CMD appeal and Collagen VI Alliance, in recent years researchers have discovered a lot about what is happening inside the cells of people with Ullrich CMD. One of the findings is that structures in the cells called mitochondria – which are the ‘batteries’ supplying energy – are not functioning correctly. Two drugs have shown promise – Omigapil and Debio 025. A company called Santhera is conducting a clinical trial of Omigapil in the USA. This trial will involve children with CMD, including Ullrich CMD.
Another possible avenue being considered for the development of therapies includes drugs that reduce ‘fibrosis’ or scarring in the muscles which is thought to be a major contributor to the muscle weakness in CMD. Losartan, a commonly prescribed medication for high blood pressure, is one possible candidate for testing in clinical trial. These approaches that target the mitochondria and fibrosis do not address the root cause of the condition so would only be able to treat some of the symptoms of the condition.
Ideally, a treatment would result in the production of properly functioning collagen in the body. Gene therapy to correct genetic mutations is being researched for other genetic conditions including other types of muscular dystrophy and if these prove to be successful it may be possible to apply this technology to the development of treatments for Ullrich CMD.
*This information comes from the website: www.mda.org.au and research papers provided by Great Ormond Street, available on request.