By Lucy Jenkins, Director of the Regional Genetics Laboratory based at Great Ormond Street Health for Children (GOSH), Prof Maria Bitner-Glindzicz, Clinical Geneticist based at the Institute of Child Health and GOSH and Dr Christin Eltze, Consultant Paediatric Neurologist and lead consultant for the Ketogenic Diet service at GOSH.

Personalised medicine represents the next generation of medicine and healthcare research. While the idea of personalised medicine is not new, emerging developments in genomics are expected to create a paradigm shift in how patients experience their healthcare journey.

Whole Genome Sequencing, which involves studying an individual’s DNA in its entirety, provides a huge step forward in the diagnostic information available. It is now possible to predict how individuals will respond to specific interventions, or identify if a person is susceptible to a certain illness. Through analysing an individual’s genetic profile, the prevention, diagnosis and treatment of a disease can be tailored towards specific individuals rather than general populations.

A growing number of researchers, healthcare professionals, and an increasing number of patients too, are calling for a more personalised approach when it comes to treatment and diagnosis.

Great Ormond Street Health for Children (GOSH) in London, U.K., is an example of a global centre that has outlined its commitment in providing the highest quality of care for its patients, by using the latest technologies and innovations, including genetic testing, to treat children with rare and complex conditions from all over the world.

Lucy Jenkins explains that through studying variations in the human genome, researchers can establish if a person may respond better to a certain drug or treatment intervention.
“In recent years, genetics and genomics has undergone a technological revolution and it is now possible to sequence the whole genome in a matter of days. As an example, through genetically testing if a person with cancer has a particular mutation in the Jak2 gene, a protein producing gene that promotes proliferation of cells, we can establish if they will respond better to one cancer treatment then another,” she says.
Similarly, this is the case with aminoglycoside antibiotics, a type of Gram-negative sepsis treatment that inhibits the spreading of bacteria through aminoglycosides binding to bacterial ribosomes. Some people have an inherited predisposition that renders them highly sensitive to the ototoxic effects of these antibiotics: aminoglycosides taken at levels that are well within the therapeutic range can result in rapid, profound, and irreversible hearing loss.
“Even a single dose of aminoglycosides in a predisposed individual can result in permanent hearing loss. This is why it is so important that we can now test for particular genetic polymorphisms. If they have that polymorphism, we can ensure they do not take the medication,” Prof Maria Bitner-Glindzicz explains.

Personalising epilepsy treatment
Dr Christin Eltze further explains that genetic testing has helped in personalising treatment for patients with epilepsy. 
“Genetic testing in a person with epilepsy can help to confirm a specific diagnosis. It may also give information about other associated neurologic or medical conditions that may arise over time. It can assist neurologists with selecting appropriate seizure medication and also with expectations regarding appropriate seizure control. Genetic information may also influence whether or not a dietary treatment, such as the ketogenic diet, might be especially appropriate,” explains Dr Eltze.

The ketogenic diet is a special high-fat, low-carbohydrate diet that helps to control seizures in some patients presenting with seizures that are difficult to control with antiepileptic medication. It is prescribed by a physician and carefully monitored by a dietitian. It is stricter than the modified Atkins diet, requiring careful measurements of calories, fluids, and proteins.
Studies have shown that this diet is particularly helpful for GLUT-1 deficiency syndrome, but also some patients with conditions including infantile spasms, tuberous sclerosis complex, Dravet syndrome, Doose syndrome, have shown good response to this form of treatment.
“Genetic testing can play an important role in the care provided to patients with epilepsy. Doctors usually prescribe the diet for children whose seizures have not responded well to other medication, but genetic testing can also play a part by confirming a certain genetic type of epilepsy that has a higher chance to respond well to the diet.”

Looking to the future

The 100,000 Genomes Project, launched in December 2014, set out to sequence 100,000 whole human genomes to help researchers and clinicians better understand, and ultimately treat, rare and inherited diseases and common cancers.

Lucy Jenkins explains that the project will sequence 100,000 genomes from around 70,000 people. Participants are National Health Service (NHS) patients with a rare disease, plus their families, and patients with cancer.

“The idea is that if you get that volume of information from a rare disease or a cancer you can start to look for parallels in changes people have to the genome that might be meaningful and we could interpret to either help with therapies for cancer or help define new genetic causes for a disease,” explains Lucy Jenkins.

“At some point the data will be available more widely so that people can look at why there are variations in the DNA, so that therapy can be targeted towards a particular patient or a particular cancer. For that reason, the data will be opened up at some point to research allowing people to find out more information about how we can target therapies or treatment,” she says.

Prof Maria Bitner-Glindzicz adds, “With undiagnosed genetic conditions, it really is a case of the more families we test, the more we can diagnose. In order to confidently say that a particular gene is likely to be the cause of a condition and not just natural variation that we see in everyone’s genes, we have to match up gene mutations and symptoms across several children to find common features. The more children we therefore have to cross check against, the more likely it is that we can find these common features and give a diagnosis."