Is personalised medicine the future?

A child with leukaemia has been treated using gene therapy, but is it hype or a step forward in medicine?

Layla’s parents were desperate. Their one year-old child had been diagnosed with leukaemia that was too aggressive to effectively treat with chemotherapy. Her mother, Lisa, said: “We didn’t want to accept palliative care and so we asked the doctors to try anything for our daughter, even if it hadn’t been tried before.”

Eager to explore all possible treatment routes, they contacted Professor Waseem Qasim at University College London, who was developing a treatment to treat acute lymphoblastic leukaemia, the specific type that Layla had. This form of leukaemia causes cancerous stem cells to release large numbers of immune cells into the blood.

The treatment Waseem Qasim was developing is known as gene therapy, which is a form of treatment that involves altering the genes in our body to combat diseases. It has been termed ‘personalised medicine’, where a specific disease can be targeted by altering specific genes that will affect it.

The concept of gene therapy was developed in the 1970s, just over 20 years after Watson and Crick discovered DNA, which is what makes up the genes in our bodies. However, progress has been incredibly slow in making this therapy a reality. While it is a simple concept, the technicalities of delivering this therapy due to the complexities the human body are great.

However, recent advances in research have led to real progress, with Layla’s story being an example of this. Waseem Qasim’s research focused on treating leukaemia by using gene therapy to modify the immune cells that fight disease in our body. In Layla’s case, donor immune cells were used, as the chemotherapy she had undergone and her young age meant she had a very depleted immune system.

The immune cells were modified in the lab to combat the cancerous cells. This was done by adding new genes to the immune cells, allowing them to recognise and attack leukaemia cells. They were also modified to avoid being attacked by Layla’s own immune system and the anti-immune system drugs used in conventional leukaemia treatment. These immune cells were then introduced into Layla’s body to begin the process of attacking the leukaemia cells.

This treatment had never been clinically trialled but Layla’s parents were willing to try it. After seven weeks of treatment, the number of cancerous leukaemia cells were depleting. Once doctors were confident that they had all all been removed, they gave her a bone marrow transplant to replace her entire blood and immune system which had been wiped out by the treatment. She is now recovering at home, but still has regular check ups at the hospital to ensure she is on track.

However, like all novel treatments, restraint must be advised when lauding it is a ground-breaking success, with Waseem Qasim adding: “We have only used this treatment on one very strong little girl, and we have to be cautious about claiming that this will be a suitable treatment option for all children.”

Mistakes made in the past with gene therapy have led to scientists proceeding with caution when claiming it to be a success. By the late 1990s the idea of personalised medicine was regarded as the future of treating genetic diseases in many scientific circles. However, unexpected consequences and the complexities of taking a gene, modifying it and inserting it into a patient resulted in many negative headlines.

The most high-profile example is the death of Jesse Gelsinger. The American teenager involved in a clinical gene therapy trial in 1999 when a severe immune reaction resulted in multi-organ failure. Jesse suffered from a rare liver disease where the lack of a gene in his body led to toxic ammonia building up, with the gene therapy aiming to counter this by inserting a copy of the required gene into his liver.

They could never determine the cause of Jesse’s death due to no blood samples dating from before his treatment remaining. However, the accepted theory is that the severe response was caused by the immune system reacting to the vessels in which the genes were transported in when delivering them to lungs. Jesse’s immune system perceived them as foreign (not components of his own body) so proceeded to attack the vessels, triggering a massive immune response.

In previous interviews, Professor James Wilson, who led the trial, has admitted that they rushed into trialling these therapy techniques due to how exciting the model of gene therapy was. “We were drawn into the simplicity of the concept. You just put the gene in,” he admitted. He added: “With what I know now, I wouldn’t have proceeded with the study.”

However, since the early noughties there have been major advances into understanding our genetic make-up, such as the completion of the Human Genome Project in 2003, which identified every single gene found within a human body. We also have developed the technologies involved in gene therapy. For example, the immune cells used in Layla’s gene therapy were altered to make them invisible to her own immune system, ensuring that what happened to Jesse did not happened to her.

These scientific and technical advances have to led to gene therapy success stories in recent years. In August, researchers at The University of Manchester restored vision in blind mice. They inserted a gene that fixed a malfunctioning protein found in eye receptors that detect brightness. They hope for human trials to begin in the next few years. There have also been advances in using gene therapy to improve disease resistance for those infected with HIV and to alleviate the symptoms of cystic fibrosis.

It is still early days in Layla’s recovery process. As this is the first time this treatment has ever been clinically trialled in a human, the long term effects and consequences are still unknown. Ashleigh, her father, reflects on this: “Even though she is well at the moment, we still don’t know what the future holds. It’s always at the back of your mind. It’s not like chickenpox that clears away, this is constant. You always have doubts.”

Nevertheless, researchers are optimistic, with Waseem Qaseem stating: “This is a landmark in the use of new gene engineering technology and the effects for this child have been staggering. If replicated, it could represent a huge step forward in treating leukaemia and other cancers.”

While the treatment is still in its infancy, research has progressed since the mistakes made at the cusp of the Millennium. With full clinical trials starting in 2016, hopefully Layla will be the first of many to be treated using this personalised medicine.

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