Ankylosing Spondylitis (AS)
Ankylosing spondylitis (AS) is the second most common type of chronic inflammatory arthritis and is characterized by pathologic new bone formation that ultimately affects bones, muscles and ligaments. This inflammatory disease is a member of the group of spondyloarthritis and can:
- Target the axial skeleton
- Involve peripheral joints and nonarticular structures
- Have a strong genetic predisposition
- Be driven by an immune reaction
- Eventually result in the fusion of the affected spine and sacroiliac joints
- Lead to complete rigidity of the spine, termed “bamboo spine”
Current attempts to diagnose AS
Patients with AS gradually develop symptoms, usually appearing first around the age of 23. Initial symptoms are chronic pain and stiffness to parts of the spine. From initial detection, it takes between 8.5-11.4 years on average to achieve a firm diagnosis of AS. The disease is also linked to uveitis via the HLA-B27 antigen and approximately 40% of AS patients also suffer from inflammation in the anterior chamber of the eye.
There is no cure for AS patients and a direct test to diagnose AS does not exist. Clinical examination via X-ray of the spine allows clinicians to identify characteristic spinal changes and sacroiliitis, but only after 8-10 years of disease onset. A genetic marker blood test for HLA-B27 is available but is not sufficiently specific to reliably diagnose AS. MRI and tomography of the sacroiliac joints is an option for earlier diagnosis but must be used in combination with other tests.
Developing novel tests for AS diagnosis and treatment
The pathogenic pathway in AS is poorly understood and therefore current treatments still focus on reducing pain and alleviating symptoms. TNF blocking agents can help to reduce inflammation, but most patients relapse immediately after treatment is stopped. Two recent independent studies indicated that non-steroidal anti-inflammatory drugs (NSAID) can decrease radiographic new bone formation. Nonetheless, better, more reliable methods of early diagnosis are urgently needed to improve patient outcome, both for selecting the right medication and for monitoring the response of patients to therapy.
In an effort to improve the situation, we have identified novel autoantigen candidates by screening well characterized AS serum samples and comparing those to healthy serum samples using our proprietary technology platform. We’re now using these highly specific autoantibody profiles to develop new diagnostic tools for earlier and more specific AS diagnosis.
CDx co-development for creating better medicines
Even using the most sensitive technology available, such as MRI and tomographic imaging, it still often takes over a decade from the time of initial onset to obtain a firm diagnosis of AS. Treatment during this window is often speculative, with no guarantee of any measurable success. As such, there is a distinct need to create diagnostic tools that can classify the disease much earlier, the likes of which would significantly inform drug development programs targeting this important and lengthy stage of disease progression.
To realize this goal, we need to discover, validate and utilize novel diagnostic biomarkers that can predict:
- disease onset earlier
- classify patients more effectively into relevant disease subgroups
- enable the informed ongoing assessment of treatment effectiveness
Our SeroTag autoantibody discovery and validation platform has the power to reveal the subtle links between disease incidence, severity and progression in different patient populations suffering from AS, providing data useful in the development of new drugs. By differentiating patients into related groups and selecting those patients most likely to benefit from treatment, our Pharma partners can speed up the development of their drug candidates and improve the chances of faster regulatory approval.