From Rare Diseases to Common Cures: the gene therapy way

Today is the ten year anniversary of Rare Disease Day and in that time courageous trial patients and their heroic doctors have been trailblazing a completely new treatment for mankind: gene therapy.

Although the first successful gene therapy treatment took place in 1990, it has only been in the last few years that we’ve begun to see the fruits of this research. With the  technology being used to treat ever more common conditions, these fruits are now stacking up to be plentiful. Without a shadow of a doubt, we have those affected by rare diseases to thank for this progress.

 PATIENT WITH the rare immune disorder, aDA SCID, during her gene therapy treatment

 PATIENT WITH the rare immune disorder, aDA SCID, during her gene therapy treatment

As many of the rarest diseases in the world are caused by a single faulty gene, the early pioneers of gene therapy decided that they would be a good place to start their research. Decades before our genetic make-up was published in The Human Genome Project, geneticists had sequenced the mutations (mistakes in the letters of patients’ DNA) responsible for a number of inherited rare diseases. A fatal condition called Adenosine -deaminase-deficient severe combined immunodeficiency (ADA-SCID), which effectively means a patient has no immune system, was one of the first diseases where the genetic mutation was clearly identified.  The next step involved spotting where the mistakes were, and figuring out a way to corrected them. Evidently dealing with just one gene seemed like the most manageable route to success. But success proved to be a long time coming and the route took some unexpected detours.

Scientists actually had little problem coming up with a way to correct the faulty gene. They compared the mutated and healthy version, saw where the mistakes were and lined up the correct sequence of human DNA letters. However, the monumental challenge that would occupy the better part of the next three decades, proved to be getting these healthy new genes into patients' cells. In short, they needed some kind of delivery vehicle to shuttle them in. Scientists pinned their hopes on using viruses as they have naturally evolved to infect human cells with their viral DNA. But the various viral delivery vehicles they first tried caused fatal responses: and it was not until last year that an ADA SCID gene therapy was finally licensed.

For three decades scientists and ADA SCID patients battled the high seas of science to get this product to market. Today similar gene therapies for a range of rare diseases and even some cancers are progressing through patient trials around the world.  

A disease is defined as rare if it affects less than 50, 000 people in Europe or less than 200 000 people in American. However, collectively, rare diseases are not rare.  They affect around 6% of the global population and there are 6 to 8000 different types of rare diseases.

Dr Rafael Yáñez-Muñoz, the Editor of Gene Therapy, has an example that really brings this home; “Six per cent of people being affected means that in your street, on the train that you use for your daily commute, in your child’s school and at the gym where you train, there will be several people affected. At the universities or research organisations where we teach and research, hundreds of people will be affected. If you look around yourself, you may see them, giving an example of endurance and determination in their struggle with daily activities that we take for granted.” 

On the face of it, research for rare diseases receives a disproportionately heavy investment (e.g. 20% share of the health budget in the UK). However, this research is very much planting the seeds for future breakthroughs in genetic medicine. Gene therapy is already reaping rewards: Parkinson's, Haemophilia, Cystic Fibrosis, Sickle Cell Anaemia  are all examples of relatively common genetic diseases that are already in patient trials, so the fruits of this research could be very far-reaching.

The tide is finally turning for gene therapy, washing over the trials and tribulations of its past. As we look to future advancing technologies like Crispr, which has the capability of editing out the multiple mutations behind more common diseases like cancer (if interested see my online article), once again, it will be people affected with rare diseases who will be trailblazing these treatments, which we all stand to benefit from.

The Rare Genomics Institute an amazing organisation that brings affected patients, families and cutting-edge scientists together: