Could Laminin be Used to Treat Duchenne Muscular Dystrophy?

Mon, 01/28/2013 - 12:40

Duchenne muscular dystrophy (DMD) is a severe muscle wasting condition, causing disability and early death. There is currently no cure or adequate treatment for DMD, but pioneering research indicates that injection of a laminin protein may prevent (or at least slow) this muscle degeneration.

Around 1 in 3,500 boys are born with DMD. Their muscles become progressively weaker, leading to restricted mobility, and death in their twenties from heart/respiratory failure. Effective therapies for DMD are urgently needed. Mutations in the dystrophin gene result in the lack of this protein in DMD patients. An understanding of the role of dystrophin in normal muscle has enabled the investigation of ways to compensate for its absence.

Immunocytochemistry/Immunofluorescence: Laminin Antibody

The cytoskeleton within myofibers (muscle cells) is connected through the sarcolemma (muscle plasma membrane) to the basal lamina (adjacent extracellular matrix). These stabilizing linkages protect the sarcolemma from the potentially damaging forces it is subjected to by muscle contraction/stretch; in the absence of sufficient mechanical reinforcement, sarcolemmal integrity is reduced and necrosis results. Dystrophin is the link between the cytoskeletal actin filaments and a transmembrane protein called dystroglycan, which itself binds to the extracellular matrix (ECM) protein laminin on the other side of the sarcolemma. A different anchoring system comprises the alpha-7 beta-1 integrin, another transmembrane protein present in the sarcolemma, bound both to laminin in the ECM and the cytoskeleton inside the cell.

Rooney et al. recently discovered that administering laminin-111 protected muscles from damage, such as that usually induced by exercise when dystrophin is missing, in the mouse model for DMD. The presence of laminin-111 (the form of laminin composed of alpha-1, beta-1 and gamma-1 chains) in muscle is normally restricted to the embryo, but it was used because it is readily available in a purified format and is similar to laminin-211 found in adult muscle. Probing with a laminin antibody (for alpha-1) in immunofluorescence (in this case, IHC with a fluorescent label) revealed that the laminin-111 was systemically delivered to muscles throughout the body following an i.p. injection. Laminin-111 was found to increase expression of alpha-7-integrin; it is thought that the alpha-7 beta-1 integrin linking system may be complementary to the dystrophin complex, and provide compensatory mechanical stability. Goudenege et al. verified these findings (including similarly using an appropriate laminin antibody to observe the distribution of laminin-111 some weeks after injection). They also demonstrated that laminin-111 improved the results of myoblast (muscle precursor cell) transplantation, a technique aiming to strengthen weakened muscle. They reported that laminin-111 increases myoblast proliferation/migration, which may address their previous problem of injected myoblasts having only a localized effect.

These important findings could lead to considerable improvements in the prognosis of this devastating disease.

  1. PMID: 19416897
  2. PMID: 11257121
  3. PMID: 20683444

Novus Biologicals offers laminin reagents for your research needs including:

Written by Carly Hammond

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