Solutions for preventing adverse reactions in cells of the nervous system in a study by the Department of Biology and Biotechnology at the University of Pavia published in Nature Communications
PAVIA. Gene therapy, which involves introducing genetic material into cells for the purpose of treating a patient, is proving very promising for the treatment of a wide range of disorders of the brain and nervous system. These include well-known diseases such as Parkinson’s and Alzheimer’s, as well as rarer diseases such as ALS, spinal muscular atrophy, X-linked adrenoleukodystrophy and Huntington’s disease. To deliver these therapies, scientists use modified viruses or other tools to transport genetic material into the body, through the bloodstream or directly into specific areas. However, recent clinical studies have found several problems in these therapeutic approaches. Some treatments do not work as hoped or sometimes can cause even serious side effects whose causes are not yet fully understood.
Professor Anna Kajaste-Rudnitski from the Department of Biology and Biotechnology at the University of Pavia together with her team of researchers pioneered the study of how the body’s natural defences, especially in individual cells, could interfere with gene therapy. The research group has previously found that cells can detect the viral tools used for gene delivery and respond by blocking treatment or causing harmful effects (https://www.embopress.org/doi/full/10.15252/emmm.201707922 https://pubmed.ncbi.nlm.nih.gov/30416070/ ).
Mainly focusing on the blood and immune system, these studies have helped to develop new ways to make gene therapies safer and more effective. However, until now it was unclear how these immune responses work in the brain. In a new study published in Nature Communications ( https://rdcu.be/eigVU), Prof. Kajaste-Rudnitski’s team, together with Dr. Angela Gritti’s group at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) at the San Raffaele Hospital in Milan, Italy, and researchers at Spark Therapeutics San Raffaele in the US, discovered that viruses commonly used in gene therapy (called adeno-associated viral vectors or AAV) can trigger harmful immune reactions in human brain cells cultured from stem cells, so as in mice.
In particular, they understood how this immune reaction works and identified drugs that can reduce this harmful response and protect brain cells in laboratory models. This discovery fills an important gap in our understanding and could lead to safer gene therapies for brain diseases. Overall, the research opens the door to more effective and safer treatments, potentially improving the lives of many people with neurological disorders.
