Clinical Trial of Daclizumab (anti-CD25) in Multiple Sclerosis
Multiple sclerosis is caused in large part by T cells attacking the myelin sheath that serves as an insulator for neurons, however other cells, such as myeloid cells, are also postulated to play a role.
Activated T cells express the protein CD25, which is the alpha chain of the IL-2 receptor. Clinically, the use of antibodies against CD25 has been reported to induce immune suppression in conditions such as transplant rejection. In fact, the anti-CD25 antibody, Daclizumab (drug name Zenapax) is approved by the FDA for prophylaxis of acute rejection in renal transplant patients for use as part of a cocktail with corticosteroids and cyclosporin.
A recent clinical trial investigated the addition of daclizumab to interferon beta in patients with multiple sclerosis that did not respond satisfactorily to interferon beta (Bielekova et al. Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 2009 Apr;66(4):483-9).
The study subjects where treated with interferon beta for three months and for another 5.5 months by the combination of interferon beta and daclizumab. If after 5.5 months of daclizumab and interferon the patients had a >75% reduction in MRI contrast enhancing lesions, then they were given treatment with daclizumab alone for an additional 10 months. If the patients did not experience a response, the dose of daclizumab was doubled.
Of 15 patients, 5 reported treatment associated adverse effects, with 2 patients having to discontinue daclizumab. 9 of the 13 patients that continued on daclizumab and interferon had disease stabilization, which was observed even after conversion to daclizumab therapy alone.
According to the authors, this study suggests that “Daclizumab monotherapy is effective in most patients who experienced persistent MS disease activity with interferon beta therapy“.
This study is very interesting because CD25 expressing cells are not only activated T cells but also T regulatory cells, therefore some caution has to be used when administering agents that target CD25 since depletion of T regulatory cells would hypothetically accelerate progression of autoimmune diseases. Nevertheless, this study supports the continued investigation of combinations between daclizumab and interferon.
Tags: cd25, daclizumab, immune modulation, interferon, multiple sclerosis
June 9th, 2009 at 7:52 pm
[...] however, are still relatively nonspecific and have adverse effects. Newer treatments such as anti-CD25 antibodies are also in clinical trials, but still are not [...]
June 10th, 2009 at 12:12 pm
[...] contrast to relatively more specific methods of blocking T cells, such as Daclizumab which blocks activated T cells (and maybe but hopefully not T regulatory cells), antilymphocyte [...]
June 11th, 2009 at 2:50 pm
[...] instead of selectively killing some specific T cells, or only killing the activated T cells (like daclizumab does), the process of using stem cells with immune depletion involves first killing ALL immune [...]
July 1st, 2009 at 4:03 am
[...] the immune response in a specific manner. This is different than other immune modulators such as anti-CD25 antibody or Tysabri which suppresses in a non-specific [...]
July 14th, 2009 at 3:23 am
[...] the immune system that is pathological. Additionally, such an approach would have advantages over non-specific immune suppressants which non-specifically shut down all T cell [...]