Hell pain and paralysis
The international medical term for ankylosing spondylitis is ankylosing spondylitis, also known as radiographic axial spondylitis. The name itself hints at what happens to patients. Ankylosing means stiff and inflexible, while spondylitis means inflammation of the spine. In this condition, inflammation and structural changes develop in the spine and joints, visible on x-ray.
Most often symptoms begin when people are in their working years, typically between 20 and 40. Some research shows men may be affected a bit more often than women. The disease is autoimmune, caused by a malfunction in the immune system. The body turns against itself, mistaking healthy cells for foreign invaders. Autoreactive T lymphocytes play a central role in this process.
In ankylosing spondylitis, the attack targets connective tissue that forms ligaments, intervertebral discs, and joint capsules. Inflammation at tendon and ligament attachment points to bone, called enthesitis, produces intense pain because nerves in these areas are highly sensitive. Over time, connective tissue can be replaced by bone. Ligaments and joints lose flexibility, and vertebrae may fuse. This process can twist the spine and progressively limit movement. The most drastic loss of motion is called ankylosis, and in severe cases, independent mobility may be lost.
Today, the primary treatment is anti-inflammatory therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed. Recently, biologic drugs have become more widely used. These are monoclonal antibodies that target inflammatory cytokines. Anti-cytokine therapies can greatly improve quality of life, reduce inflammation, and ease pain. However, they do not halt the underlying disease, so tissue damage can continue, albeit at a slower pace.
Cytokines also serve protective roles in the immune system. Anti-cytokine medications can suppress immune function, increasing infection risk. With long-term use, the body may become less responsive to the drug, limiting effectiveness. These factors constrain how well modern autoimmune disease therapies work over time.
Experts describe a shift in approach driven by bioinformatics. By analyzing the diversity of T cells in patients and mapping the structures of T cell receptors linked to the disease, researchers aim to identify disease-driving immune cells. Unlike cancer cells, immune cells remain relatively stable, making it possible to target specific pathological cells without crippling the entire immune system. The result is a monoclonal antibody designed to attack those cells while preserving overall immune function.
new approach
The idea of a new path for treating ankylosing spondylitis emerged nearly two decades ago, according to leading Russian researchers. In 2019, a center for high-precision genetic technologies and biomedicine was established in Russia as part of a broader effort to build world-class scientific institutes. A research consortium included scientists from the National Research Medical University NI Pirogov, the Institute of Bioorganic Chemistry, and senior researchers from the Russian Academy of Sciences, as well as partners from a major medical center and a national biotechnology company. This collaboration accelerated targeted research in this field. The scope of the work is enormous and ongoing.
Researchers collected patient samples and analyzed millions of lymphocyte sequences using next-generation sequencing. Specialized computer programs were created to process and interpret these vast data sets, enabling new insights that had not been possible before.
According to Lukyanov, this collaboration produced a distinctive, forward-looking treatment strategy for ankylosing spondylitis. Based on this approach, BIOCAD developed a therapeutic antibody named BCD-180, with the international nonproprietary name seniprutug. This stands as a clear example of productive cooperation between academic science and biotechnology in Russia.
As the project progressed, discussions emphasized the need for expertise in patent law, regulation, and technology. The team benefited from a strong industrial partner in the genomics center, BIOCAD, which believed in the concept and supported its development. This is noted as a rare instance of a pioneering approach gaining global attention.
patient renewal
BCD-180, also known as seniprutug, is a monoclonal antibody targeting the T cell receptor segment TRBV9. In ankylosing spondylitis, disease-driving T cells often carry this receptor and attack body tissues, fueling disease progression.
According to BIOCAD’s vice president for early development and research, the drug not only dampens inflammation but also addresses the root cause. Blocking the full cascade of inflammatory signals could allow patients to stay on treatment longer without losing effectiveness, he notes. The hope is that the therapy will be sustainable over time without leading to desensitization.
Crucially, the treatment aims to stop not just disease progression but also the potential recurrence of symptoms. If successful, it could halt structural changes in the musculoskeletal system and prevent new flare-ups—an outcome not seen with prior therapies.
A case highlighted in Nature Medicine describes a 60-year-old patient who achieved long-term improvement with seniprutug after years of traditional therapies. The patient had been diagnosed in 1986, and prior options included stem cell transplantation and joint replacement. After initiating BCD-180, a marked drop in TRBV9+ T cells in the peripheral blood was observed, while other T cell subsets remained unaffected.
Over subsequent years, the patient reported reduced pain and stiffness and began physical therapy, previously hindered by intense joint pain. Anti-cytokine drugs were reduced or stopped as mobility improved.
Current use involves administering BCD-180 every four months, with no serious adverse effects reported and four years of remission. X-ray imaging showed a regression of previously enlarging bone growths. The drug has now entered its third and final phase of clinical trials with approval to commence in axial spondyloarthritis patients in certain jurisdictions.
future perspective
Experts see the potential for BCD-180 to benefit most ankylosing spondylitis patients carrying the HLA-B27 gene, a group estimated at roughly 95 to 97 percent of cases. This genetic link also appears in related conditions such as psoriatic arthritis and uveitis, among others.
The researchers hope the molecule could treat the entire HLA-B27-associated disease spectrum. The core achievement lies in identifying autoreactive T cells specific to each condition, opening the door to targeted therapies for a range of autoimmune diseases. This work could signal the start of a new platform for autoimmune treatment.
The same approach has been explored for type 1 diabetes, another autoimmune disease that often affects children and can impact multiple body systems. A monoclonal antibody developed in collaboration with scientists from NI Pirogov is entering clinical testing after regulatory approval. While promising, experts acknowledge there is much work ahead and stress that breakthroughs of this kind require rigorous validation before they become standard care.
Experts emphasize that progress hinges on continued research and responsible communication with the public. The path forward is challenging, but the potential to address major autoimmune diseases with specific immune-targeted therapies could reshape treatment landscapes worldwide.