Gene therapy trials against rheumatoid arthritis
Rheumatoid arthritis is an autoimmune inflammatory disease that occurs about three times more frequently in women than in men. It mainly affects the joints, which typically become swollen and painful. It is a chronic disease, for which there is no definitive cure. The therapies currently available are aimed at reducing inflammation and the resulting symptoms, with the goal of improving the quality of life of patients. However, several types of gene therapies are being studied that are aimed at counteracting autoimmune mechanisms, i.e. those by which the immune system attacks the tissues of the joints, causing the disease.
Rheumatoid arthritis numbersAccording to data from the Istituto Superiore di Sanità, updated in February 2023, it is estimated that in Italy there are between 200,000 and 300,000 people suffering from rheumatoid arthritis, approximately 0.5% of the population. The disease can appear at any age, but in most cases it occurs between the ages of 40 and 60. The evolution of the disease varies greatly from individual to individual, but very often it is characterized by alternating acute phases and moments in which the symptoms are almost absent. In addition to the joints, rheumatoid arthritis can also affect various internal organs, with inflammation for example of the membrane that covers the heart (pericarditis), blood vessels (vasculitis), the pulmonary membrane (pleurisy), and the lacrimal and salivary glands.
Therapies already in use against rheumatoid arthritisThe treatments currently available for rheumatoid arthritis aim to reduce inflammation to limit joint damage and the disability that can result. There are currently two main categories of drugs: symptomatic and disease-modifying. The former include nonsteroidal anti-inflammatory drugs (such as ketoprofen, ibuprofen, and so on) and corticosteroids.
The second category is made up of so-called disease-modifying anti-rheumatic drugs (DMARDs), of which methotrexate is one of the most widely used. These are drugs that usually significantly reduce symptoms and improve joint function, although they may take several months to become effective. In addition, they can cause side effects such as diarrhea, loss of appetite, headaches, and may affect liver function.
Finally, in recent years, so-called biological drugs have emerged, which target specific cells of the immune system. They are usually used when traditional drugs are not effective, alone or in co-administration with the latter.
The Promise of Gene TherapiesAs reported in a Medscape article that takes stock of this research front – still considered to be in its infancy and entirely experimental – several gene therapies for rheumatoid arthritis being studied in the United States are based on the Crispr/Cas9 gene editing technique. In general, this is a system that allows you to modify a cell's genome by cutting the DNA at a specific sequence, with the aim of eliminating or replacing a certain fragment.
An example of the use of this technique in the context of rheumatoid arthritis is a therapy designed to modify an allele of the Hla-Drb1 gene that increases the risk of developing severe forms of the disease. In practice, explains Medscape , which interviewed one of the scientists involved in the project, it would involve taking stem cells from the bone marrow of sick patients, modifying the allele in question using Crispr/Cas9, and then re-infusing the engineered cells into the same patient. The latter, maturing and specializing, should then generate immune system cells that are not self-reactive and that slowly replace the unmodified ones. The first clinical study could start as early as next year.
Another example involves the use of Crispr/Cas9 to create cells that are able to detect the levels of pro-inflammatory cytokines produced by the body to trigger a proportional release of molecules that counteract inflammation. The cells, then allocated to a special cartilage support and implanted, would become a sort of internal "thermometer" capable of activating the therapeutic response only to the extent necessary and when actually needed. In this case, the approach is being studied on animal models and is actually designed for the treatment of osteoarthritis - a disease that is not autoimmune in nature and therefore different from rheumatoid arthritis, with which it nevertheless shares the inflammatory aspect, as the authors of the research explain.
The latest studies for the use against rheumatoid arthritis and osteoarthritis are further expanding research in the field of advanced therapies in rheumatology. For example, the experimental use of Car-T cell therapies against systemic lupus erythematosus in both adults and some children is also recent.
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