ATL1102 for Duchenne muscular dystrophy
Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a rare X-linked genetic disease which affects approximately one in every 3,500 to 5,000 males worldwide. DMD is caused because of a mutation in the muscle dystrophin gene leading to severe progressive muscle loss and function. Muscle weakness becomes increasingly noticeable between the ages of 3 and 5 and wheelchair use generally occurs in the very early teenage years. During adolescence respiratory and cardiac muscles weaken and cognitive dysfunction emerge leading to serious, life-threatening complications. A key challenge in the management of DMD patients is to reduce the inflammation that exacerbates the muscle damage. Corticosteroids are the only approved treatments for muscle inflammation; however, they are not well tolerated, do not sufficiently suppress muscle inflammation, and have serious side effects. As a result, there is an acknowledged high unmet need for new therapeutic approaches for the treatment of inflammation associated with DMD.
ATL1102
ATL1102 is an antisense oligonucleotide therapy targeting Very Late Antigen-4 (VLA4). ATL1102 works by inhibiting CD49d (a subunit of VLA-4) expression on lymphocytes, reducing inflammation.
ATL1102’s mechanism of action is well validated and clearly understood.
Duchenne muscular dystrophy (DMD) is an X-linked disease that affects 1 in 3500 to 5000 live male births. 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 and 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 result, there is an acknowledged high unmet need for new therapeutic approaches for the treatment of inflammation associated with DMD.
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 result, there is an acknowledged high unmet 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.
The Company is conducting a Phase II clinical trial of ATL1102 in DMD patients at sites in UK, Bulgaria, Turkey, Serbia and Australia. Click below for more details:
