Spinal Muscular Atrophy

InFocus

Dear Readers

This special “In Focus” report is the second in a series of MDA comprehensive reports about the latest in neuromuscular disease research. (The first,”Drug Development Progress,” ran in Winter 2009.)

This report provides an overview of spinal muscular atrophy (SMA), a disease in which a loss of nerve cells in the spinal cord causes weakness or paralysis of variable severity.

Chromosome-5-linked SMA, by far the most common form of the disease, lends itself well to certain therapeutic interventions because of its unusual genetics. In contrast to the situation in many other genetic diseases, everyone with this type of SMA makes at least a small amount of the necessary protein in which they’re deficient, called SMN. That makes it easier to devise strategies to increase SMN levels further, and easier for the immune system to tolerate the increase than in many other disorders.

Although a great deal of SMA research is focused on increasing SMN levels, investigators don’t yet know whether doing so after the onset of the disease will rescue nerve cells. Therefore, some researchers are pursuing alternatives to SMN-based strategies.

This In Focus special section (located in the center of Quest for easy removal) includes:

• “Fast Facts” about SMA

• An update on state-of-the-art SMA research, much of it supported by MDA

• Information about the SMA patient registry

• Information about the SMA Standards of Care guidelines

To learn more about SMA, visit www. mda.org/publications or call your local MDA office at (800) 572-1717.

Fast Facts

MDA’s three-year commitment for

SMA research as of January 2009 is $5,207,042, divided across 27 grants. The Association has allocated $32,287,834 to SMA research since 1950.

SMA is caused by a deficiency of a motor neuron protein called SMN (survival of motor neurons). This deficiency results when there is a faulty gene on chromosome 5.

SMA causes a loss of nerve cells (motor neurons) in the spinal cord.

One in every 40 people carries the gene flaw that causes SMA. Both parents must carry the gene flaw for SMA to be passed on; each of their children has a 25 percent change of developing SMA.

SMA is most commonly divided into types 1 through 4. (Sometimes further subdivisions, such as type 2a, 2b, etc., are used to indicate gradations of severity.) These types vary in age of onset and intensity of symptoms, but all are due to mutations in the SMN gene on chromosome 5. SMA types are defined, in part, by a person’s age at symptom onset and the highest motor milestone achieved (i.e., sitting, standing, walking).

Types of SMA

SMA type 1

(infantile-onset, Werdnig-Hoffmann disease)

The most severe form of SMA, type 1 is evident in infants between birth and 6 months old. These children never achieve independent sitting. At present, 50 percent of babies with type 1 SMA die before their second birthday.

Some physicians refer to the most

The age of onset and severity of SMA are highly variable.

severe cases of infantile-onset SMA as type 0. they reserve this designation for babies who are born with severe weakness and die during the first month of life.

SMA Type 2
(intermediate SMA)
Type 2 typically affects babies before
18 months of age. Children may be
able to sit unaided or stand with sup-
port. They are at increased risk for
complications from respiratory infec-
tions, and life span is often shortened.

SMA Type 3
(juvenile SMA, Kugelberg-Welander
disease)
Type 3 is the mildest form of child-
hood-onset SMA. It strikes as early as
18 months and as late as adolescence.
Children with type 3 have variable
degrees of weakness but are able to

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