ATL1102 is an antisense inhibitor of CD49d, a subunit of VLA-4 (Very Late Antigen-4)
DMD is caused by a mutation in the muscle dystrophin gene leading to severe progressive muscle loss and premature death. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 to 5,000 males worldwide. A key challenge in the management of DMD patients is to reduce the inflammation that exacerbates the muscle fibre damage. Corticosteroids are the only approved treatments for muscle inflammation, however they do not sufficiently suppress muscle inflammation, are not well tolerated and have serious side effects including adversely affecting growth rate. As a consequence, there is an acknowledged high need for new therapeutic approaches for the treatment of inflammation associated with DMD.
Recently published clinical research on DMD patients has shown that patients who have a greater number of T cells (immune cells) in the blood that express high levels of CD49d (CD49dhiT-cell) are associated with both more severe and rapid disease progression, with an increase in the number of CD49dhi T cells associated with reduced walking capacity. Corticosteroids did not reduce these CD49dhi T cells. ATL1102 has been shown to block CD49d (VLA-4) expression on lymphocytes (including T cells), reduce immune cell numbers (including T cells), and to be highly effective in reducing inflammatory brain lesions in MS patients after only 8 weeks of dosing.
A clinical trial of ATL1102 is planned to be undertaken at the Royal Children’s Hospital (RCH) in Melbourne in boys with DMD.
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What is DMD?
Duchenne Muscular Dystrophy (DMD) is an X-linked disease that affects 1 in 3600 to 6000 live male births (Bushby et al, 2010). DMD occurs as a result of mutations in the dystrophin gene which causes reduction in or absence of the dystrophin protein. Children with DMD have dystrophin deficient muscles and are susceptible to contraction induced injury to muscle that triggers the immune system which exacerbates muscle damage (Pinto Mariz, 2015). Ongoing deterioration in muscle strength affects lower limbs leading to impaired mobility, and also affects upper limbs, leading to further loss of function and self-care ability. The need for wheelchair use can occur in early teenage years, with respiratory, cardiac, cognitive dysfunction also emerging. With no intervention, the mean age of life is approximately 19 years. The management of the inflammation associated with DMD is currently addressed via the use of corticosteroids, however they are acknowledged as providing insufficient efficacy and are associated with significant side effects. As a consequence, there is an acknowledged high need for new therapeutic approaches for the treatment of inflammation associated with DMD.