VLA-4 is a receptor on the surface of lymphocytes (a particular class of immune cells) which is important in immune cell adhesion to blood vessel walls and subsequent migration of lymphocytes into tissue – a key event in inflammatory diseases.
In inflammation, white blood cells (leukocytes) move out of the bloodstream into the inflamed tissue, for example, the Central Nervous System (CNS) in MS, and the lung airways in asthma. The inhibition of VLA-4 may prevent white blood cells from entering sites of inflammation, thereby slowing progression of the disease. VLA-4 is a clinically validated target in the treatment of MS. Antisense inhibition of VLA-4 has demonstrated positive effects in a number of animal models of inflammatory disease including MS with the MS animal data having been published in a peer reviewed scientific journal.
The company successfully completed a Phase IIa efficacy and safety trial, significantly reducing the number of MRI lesions in patients with multiple sclerosis and has also completed a toxicology study to support a potential future Phase IIb of ATL1102 in MS patients.
For more details and updates please refer to specific company announcements.
What is Multiple Sclerosis?
Existing & Future Therapy for Multiple Sclerosis
There is no known cure for MS – the goals of therapy are to improve recovery from attacks, to prevent or lessen the number of relapses and their severity, and to reduce disease progression.
Steroids were the principal medication for MS – while steroids cannot affect the progression of MS, they can reduce the duration of attacks. The US FDA has approved several drugs: interferon beta-1a, interferon beta-1b and glatiramer acetate which have been shown to reduce relapse rates.
The beta-interferons are the first choice treatment in patients. However there is still a number of unresolved issues including long-term effects, and the occurrence and relevance of neutralizing antibodies.
Tysabri® (natalizumab) a monoclonal antibody which targets the immune system protein (VLA-4), has been approved in the US and Europe as a monotherapy treatment for relapsing forms of multiple sclerosis (MS) to slow the progression of disability and reduce the frequency of clinical relapses. The drug has been associated with causing progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal, demyelinating disease of the central nervous system. This has lead to the drug’s restricted indication in the US and Europe.
There is clearly a need to create more effective and safer treatments for Multiple Sclerosis and consequently there are a number of new therapies under development.