We usually move around our day without thinking about the way our joints and spine work. But what if moving around is as difficult as solving mathematical equations? 

                            Distance x joint movement = Pain

For people with osteoarthritis (OA) and chronic low back pain, moving around becomes a daily struggle due to pain. Almost everyone of us knows someone who struggles from knee pain or lower back pain. Maybe you yourself also have problems walking or doing everyday activities smoothly? Most of the time, these struggles are caused by damage to the knees or spine. In our research, we are addressing these issues to help make your life easier, because we are trying to find new treatments for Chronic Lower Back Pain and Osteoarthritis.

Chronic Lower Back Pain is caused by the degradation of the intervertebral disc which is the soft buffer between the bony parts of your spine. Osteoarthritis is a disease of the joints. It can affect all parts of the joint and most commonly hips and knees. Here the cartilage, the smooth surface of the joint, is destroyed. Both diseases can cause a lot of pain and can hinder your ability to move and do everyday tasks. At the moment, available treatments are only able to reduce the pain or the inflammation, but there is no treatment to  stop the degradation or help repair cartilage or the intervertebral disc.

In CARTHAGO we will try to stimulate both tissues to regenerate. The aim is to stimulate the cells inside the tissues to do the job. We do this by inhibiting the production of inflammatory factors that cause tissue breakdown and by stimulating the production of growth factors that induce repair.

Non viral gene therapy as novel and safe approach for OA and CLBP

In our research, we are using messenger RNA (mRNA) and Antisense Oligonucleotides (ASOs) as a form of gene therapy. What is gene therapy? To answer this question we need to talk about our genetic material. Our genetic information is stored in the DNA (deoxyribonucleic acid) as genes in the nucleus of our cells. This information needs to be converted into proteins, which are responsible for all biological functions in the cells and also have a relationship with diseases. In this process, we need an intermediary called messenger RNA (ribonucleic acid) (mRNA), which carries the genetic information from the DNA into the sites of the cell where protein production takes place. The transmission of this information from DNA to mRNA is called ‘transcription’, and from mRNA to proteins is called ‘translation’ (Figure). Gene therapy is basically the ‘adjustment’ or modification of the genetic material in cells. In our projects we use two medicines for this; to be precise, mRNA and siRNA (small interfering RNA). These medicines can give the cartilage cell new instructions to make or not make certain proteins that play a role in the disease. While mRNAs intermediates the production of certain good / protective proteins, siRNAs are responsible for blocking the production of bad / harmful proteins. RNA medicines are safer because they act on a later stage of the genetic flow described above, and do not induce permanent changes in the DNA where all our genetic information is stored. This way, we are able to slow down or even stop the disease progression.

Challenge of CARTHAGO: delivery of mRNA and siRNA to the cell

Cartilage and disc tissue is very dense and has no blood vessels, so delivery of RNA and siRNA is a challenge. This issue is addressed in the scope of several so-called work packages that focus around specific aspects of the research: Cell delivery and efficient gene modulation; Improving drug delivery to tissues; Cartilage and disc repair in tissue and organ culture; Responsible research and innovation