SMA standard of care committee releases disease
management guidelines

Anew “consensus statement” on clinical care in spinal muscular atrophy (SMA), published in the August issue of the Journal of Child Neurology, aims to improve and standardize the management of this disease with respect to diagnosis, pulmonary care, gastrointestinal and nutritional issues, orthopedics and rehabilitation, and end-of-life decisions.

Establishing standards of SMA care was identified as a priority by a patient advocacy group of the International

Coordinating Committee (ICC) for Spinal Muscular Atrophy

Clinical Trials. This committee was formed in January 2005 under the auspices of the National Institutes of Health

(NIH).

Discussions at an NIH-sponsored conference in 2004, in which the goal was to formulate strategies for future clinical trials in SMA, revealed wide variations in medical practices in this disease and the need to unify these for the benefit of patients and for the conduct of future therapeutic trials. MDA supported the forming of a new SMA Standard of Care

Committee through the ICC’s patient advocacy group.

The committee divided SMA patients into “nonsitters,” “sitters” and “walkers” and addressed the care needs of the three groups separately and in detail.

Some of the group’s general conclusions are that even young children with SMA should be offered independent mobility and activities of daily living, including play; that walking should be encouraged, with the use of appropriate assistive devices and orthotics; that spinal orthoses (back braces) may provide support but don’t prevent progression of spinal curvatures and may impair breathing; that surgery for scoliosis (spinal curvature) appears to benefit patients who survive beyond age 2 when curves are severe and progressive; that scoliosis surgery should be performed while pulmonary function is adequate; and that special preoperative respiratory care and neurological monitoring during surgery are desirable.

For more about the care guidelines, see “SMA: Committee Presents Clinical Care Guidelines” in Quest Extra ( www.mda.org/publications/quest/extra) or contact your local MDA office and request a copy of the Quest Extra article. You can read the entire consensus statement at http://jcn.sagepub.com/cgi/reprint/22/8/1027.

by Margaret Wahl

Utrophin gene therapy
benefits mice with DMD

Injecting genes for the muscle protein utrophin may be a viable strategy to pursue for treating Duchenne muscular dystrophy (DMD), say researchers at McGill University in Montreal.

MDA grantees George Karpati, Basil Petrof and Josephine Nalbantoglu were part of a team that injected genes for utrophin into the leg muscles of mice missing the closely related dystrophin protein. These dystrophin-deficient mice have a disease resembling human DMD.

The advantage to injecting utrophin instead of dystrophin genes is that the immune systems of at least some children and adolescents may reject the new dystrophin as a foreign protein, while they will almost certainly accept extra utrophin, since people with DMD already make utrophin, and it won’t be foreign to them.

Newborn and adult mice showed evidence of utrophin production in the injected muscles, as well as better resistance to contraction-related damage and in some cases better force generation than on the uninjected side of the body. However, in both groups, the beneficial effects diminished over the course of a few months to a year after injection.

“A critical issue is to determine the minimum amount of utrophin that is sufficient to successfully ‘pinch-hit’ for dystrophin,” Karpati said, noting that utrophin is normally found in muscle fibers only at the places where they intersect with nerve fibers (the synapse) and that utrophin throughout the fiber membrane will be necessary to successfully treat DMD.

The other problem that must be solved is “the substantial decline of the amount of extrasynaptic [outside the

synapse] utrophin over time,” Karpati added. He said it does not appear to be a problem of immune system rejection.

The authors, who published their results online July 31 in Molecular Therapy, say that utrophin therapy might be optimized by combining utrophin gene transfer with a compound that increases protein production from the patient’s own utrophin genes.

MDA is supporting research on the latter strategy (see “ID of Utrophin Brake,” Research Updates, September-October), as well as a clinical trial to test the effects of a muscle injection of dystrophin genes into boys with DMD.

Excess of mu-crystallin
protein added to
hypotheses about FSHD

An excess of the protein known as mu-crystallin has been identified as a new addition to the array of hypotheses about the molecular basis of facioscapulohumeral muscular dystrophy (FSHD). (See “Impossible Things,” March-April.) The mu-crystallin findings add to and don’t necessarily contradict any of the existing FSHD hypotheses.

MDA grantee Robert Bloch at the University of Maryland School of Medicine, and colleagues, found much higher levels of the mu-crystallin protein