Precision Medicine

Tailored Therapies for Everyone

December 09, 2019

Treating diseases earlier, gentler and more effectively: that’s the promise of what is known as “individualised” – or sometimes “personalised” – medicine. It aims to take into account a wide range of individual factors – be they our genetic make-up, lifestyle, gender or age – that influence our health and the possible courses a disease may take. [1] In this way, the right medication can be found or the treatment can be fine-tuned to the cause of a disease and targeted precisely within the body.

Using various examples, we’ll explain how research into tailor-made medicine is carried out and what is already possible today. Which of the new findings might possibly help improve the treatment of certain diseases?

1. Curing HIV with gene therapy?

In order to infect human cells, HIV needs an entry point. The latter is a protein called CCR5, which is located on certain defence cells (immune cells) in the body. However, as the result of a genetic disorder, some people don’t produce this protein, while in other cases the protein has lost its function: HIV then finds itself no longer in a position to attack such people’s cells. Scientists and doctors are therefore looking into ways to modify the defence cells of infected people in such a way that HIV can no longer dock – just as it is unable to do so in the people with the genetic disorder. This can be achieved, for example, by transplanting the bone marrow of donors carrying this genetic disorder. However, since this therapy is risky – and finding suitable donors is also difficult – it has so far only been used on two HIV patients. [3] You can find out more about this therapy here: [https://www.aerzteblatt.de/tre...].

In autumn 2019, Chinese researchers reported on the case of an HIV-infected person who had received a transplant of stem cells that lacked the CCR5 gene. What was so special about it is that the stem cells hadn’t been donated by people with a genetic disorder. The genes of the donated stem cells had rather been deactivated in the laboratory with the help of gene scissors. Although it wasn’t possible to cure the HIV-infected person, the genetically modified stem cells successfully settled in the bone marrow. They developed into different kinds of blood cells without losing their newly acquired feature. [4] Professor Dr Gerd Fätkenheuer, Head of the Department of Infectiology at the Clinic I for Internal Medicine of the University Hospital Cologne, and Chairman of the German Society for Infectiology (DGI), says: “The most important message, in my opinion, is that it was the first time that a technology involving gene scissors had been tried out on a patient and that the latter was able to tolerate the procedure without suffering serious side effects. I would assume that there are still ways in which the procedure’s application can be optimised.” [5]

You can read more about healing HIV here: [https://www.zeit.de/wissen/ges...].

2. Antibodies stopping bladder cancer

The human immune system is able to distinguish cancer cells from normal body cells and fight them. This is how it works: the cancer cells release special proteins. Certain cells of the defence system transport these proteins to the lymph nodes where they are presented to special defence cells. If the cancer cells recognise them as dangerous, the defence cells become active. They multiply and migrate to the tumour via the bloodstream in order to fight the cancer cells.

However, some cancer cells manage to escape the immune defence. [6] They slow down the defence cells with the help of a protein. In the case of bladder cancer, for example, it’s a protein called PD-L1 (Programmed Death Ligand 1). It blocks the defence cells on the cell surface at a control point known as an immune checkpoint. Certain drugs, so-called immune checkpoint inhibitors, are brought in to prevent this from happening. As a consequence, the tumour-fighting defence cells remain active. So far, two such drugs have been approved for the treatment of bladder cancer in Europe. [7][8][9]

More information about the treatment of bladder cancer with checkpoint inhibitors can be found here: [https://www.aerzteblatt.de/arc...].

3. Using the power of the immune system to fight blood cancer

Our immune system protects us from bacteria or viruses and fights damaged cells, such as cells that have developed into cancer cells. But cancer cells often make themselves “invisible” or “inhibit” the immune system. With the help of precision medicine, scientists and doctors have found a way to fight these tumour cells. In the so-called CAR-T cell therapy, the white blood cells (T cells) from a patient’s blood are modified in the laboratory to enable them to recognise and destroy the cancer cells. The modified cells have a receptor (“chimeric antigen receptor”, abbreviated CAR) with the help of which they dock onto a molecule of the cancer cells.

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Precision medicine is already being used for certain forms of leukaemia.

Photo: Dr_Microbe/iStock

The greatest success with this therapy has so far been achieved in patients with particular types of leukaemia. Emily Whitehead was the first child worldwide to receive this treatment. The then six-year-old was diagnosed with lymphoblastic leukaemia at a stage that was no longer curable with conventional methods (more information about the disease can be found here). After undergoing a CAR-T cell therapy, she has been tumour-free since 2012. [10] As some of the patients receiving the treatment suffered considerable side effects, it has only been approved for use if at least two other cancer therapies (such as radiation or chemotherapy) have failed to be effective. [11] One of the possible side effects is the so-called cytokine storm (also known as cytokine release syndrome, CRS), which is caused by the CAR-T cells triggering a massive release of immune messenger substances leading to severe flu symptoms such as high fever and chills.

So far, scientists and doctors have used the therapy against various types of blood cancer cells. However, the method is ineffective in fighting tumours such as those occurring in breast, lung or skin cancer. That’s why researchers are currently working on developing tailored therapies for these diseases.

4. Computer-aided risk assessment

How high is the risk of developing cardiac arrhythmia? In the future, doctors could be able to assess with the help of personalised computer models whether patients are at risk of developing so-called (atypical) atrial flutter. In this condition, the atria of the heart contract at an unusually fast pace. As a consequence, patients show palpitations, shortness of breath and weakness. The condition also increases the risk of suffering a stroke (you can find out more about atrial flutter here: [https://www.herzklappenhilfe.d...]).

Researchers based in the southern German cities of Freiburg and Karlsruhe are currently developing a method to image individual models of the heart on computers. With the help of these models, they can predict whether, and where, certain electrical excitations typical for this disease could occur in the atria. [12][13]

According to the scientists, this method would also make possible the advance assessment of the effects of therapies in individual patients. That’s because computer models can help simulate new therapies without posing any risks to the patients themselves. As part of this method, researchers also factor in parameters such as the sizes and shapes of individual patients’ hearts, thereby determining the possible risks and effects of individualised treatments. For this purpose, they use imaging techniques such as magnetic resonance imaging. In addition, the electrical activity of the heart is recorded by electrocardiogram (ECG) (read more about this method here:[https://www.stiftung-gesundhei...])

5. Tailor-made treatment for depression

Magnetic resonance imaging is also used in the treatment of depression. Until now, being able to determine immediately the right therapy for a patient hasn’t been easy. After their initial treatment, only a third of patients fully recover, while the majority need several attempts to get them back to health. [14] American scientists have discovered a brain signal that could indicate whether patients would be better treated with medication or psychotherapy. [15]

They took pictures of the brains of their research participants, who were all suffering from severe depression for the first time. In the next step, the patients were randomly prescribed either special medication (read more about it here: [https://www.deutsche-depressio...]) or a so-called cognitive behavioural therapy (read more about it here: [https://www.verhaltenstherapie...]).

During their research, it was found that patients in whom certain brain regions interact particularly well at resting state are more likely to benefit from behavioural therapy. With other patients, medication seemed to alleviate the symptoms better. Consequently, the researchers are pleading for further research to investigate more thoroughly the link they discovered. One day, brain scans might be able to help tailor individual therapies to individual patients as quickly as possible. [16]

Sources and bibliography

[1] https://www.bmbf.de/de/individ...

[2] https://www.bundestag.de/resou...

[3] https://www.nature.com/article...

[4] https://www.nejm.org/doi/full/...

[5] https://deutsch.medscape.com/a...

[6] https://www.roche.de/pharma/fo...

[7] https://www.cancer.gov/news-ev...

[8] https://www.cancer.gov/news-ev...

[9] https://www.ema.europa.eu/en/n...

[10] https://www.aerzteblatt.de/arc...

[11] https://www.vfa-bio.de/vb-de/a...