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British government project may lead to custom treatments

Major genomics program underway

by

Kyodo

A revolutionary project by the British government will get fully under way in 2015 to realize “personalized medicine” for cancers and rare diseases by analyzing as many as 100,000 genomes from patients and their relatives.

The project is aimed at promptly detecting mutations in genes that cause diseases and pinpointing their origins. It will enable the development of new treatments and drugs matching the individual nature of diseases.

A genome is a set of genetic information handed down from parents to offspring and is recorded in a double helix-structured deoxyribonucleic acid (DNA).

In 2003, American, European and Japanese scientists completed mapping the human genome, which has 3 billion pairs of bases. While more than 10 years and an estimated $3 billion were spent to sequence the DNA of one person, the equipment adopted by the British project can now transcribe 18,000 human genomes a year for $1,000 each.

With technological advances, genetics, or the study of the way particular features or diseases are inherited through genes passed down from one generation to the next, is nearing full-scale application to medical treatment.

Alysia Sherley-Price, an 11-year-old girl from Hampshire who enjoys music and playing ball, was found to have a rare mutation in the gene STXBP1. Alysia has motor skills matching her age, but is mentally 5 years old or so because the mutation hampers the neurotransmitters in her brain. The diagnosis gave her family a sense of optimism.

“We actually needed a diagnosis, so we could research it and see what can help her,” said Alysia’s mother Stephanie, a nurse.

Stephanie, 42, became aware of Alysia’s delayed development before her first birthday. Alysia was confirmed with global developmental delay, a term that describes delays in language, cognitive and many other or all skills, at 21 months old.

Alysia went through numerous medical examinations throughout her life to determine whether her development delay was attributable to brain damage, a difficult pregnancy or protective injections. In 2013 genomics eventually found Alysia’s genetic mutation.

The discovery is a “move forward,” said Alysia’s father Edward, a 44-year-old business manager. “Lots of questions we had before, are now answered,” he said, expressing hope that effective new drugs can be developed by utilizing data collected from a large number of patients like Alysia.

A lot of people are concerned that a “Big Brother Society,” as described in Gorge Orwell’s futuristic novel “1984,” will be created if the government holds genetic and other personal information, Edward said. “But really, in our view, it’s a health issue, it’s a health screening.”

While people who cooperated with research prior to the 100,000 Genomes Project, such as the Sherley-Prices, pin hopes on advances in treatment of difficult diseases, they also worry because genomics can also uncover disease risks in offspring.

Kathryn Graham, 53, from Knebworth, Hertfordshire, is a former elementary school teacher who retired because she suffered from a disease called idiopathic pulmonary arterial hypertension.

The disease, which causes increased blood pressure in the pulmonary artery, in some cases occurs due to genetic mutations.

Graham’s health began deteriorating rapidly after giving birth to her second daughter.

“Climbing the stairs could feel like conquering Everest,” she said.

Her condition was classed as “end stage,” progressive and incurable without a heart and lung transplant.

Graham worried that if her disease was the result of genetic mutations, her two daughters might have inherited them. She told them of the possibility when they were 18 and 16 years old.

At the daughters’ urging, Graham accepted genetic testing, which found in 2013 that she did not have misprinted genes, a huge relief for her family.

Graham also had a heart and lung transplant in the same year, something that has enabled her to “run up the stairs now.”

Her 22-year-old elder daughter, Sarah, will marry in June.

If Graham had been found to have misprinted genes, the daughters may have given up on future childbirth, she said, adding that it would be unbearable to see her children in the same situation as hers.

“I think I could cope with it being me, but not my children,” she said.

Even if genomics becomes widely practiced, nobody should be “forced into” it and there should be choices for people, Graham said.

“A lot of patients don’t want to know (if they have misprinted genes) because they don’t want to spend all their lives worrying,” she said.

The use of genetic information in huge quantities will totally upset the conventional method of treatment in which doctors prescribe the same drug for patients with the same symptoms, instead enabling them to find an optimum, personalized treatment for each patient.

Sir John Chisholm, executive chair of Genomics England, a company wholly owned by the British government and charged with conducting the project to sequence 100,000 whole genomes, forecast that the day will come when computers check types of disease from a patient’s genome and clinical data and produce a prescription for the patient’s doctor.

They will also calculate the inherited risk of diseases such as diabetes and help doctors work out instructions for eating and other lifestyle habits so as to prevent them, according to Chisholm.

When a baby is born, if the parents agree, a heel prick is conducted to collect a small sample of blood for testing for a small number of serious disabilities, Chisholm said.

“In principle, the same could be done, and the genome could be taken from that,” he continued. “So at birth, then, every child would have their whole genome recorded, and that would go throughout their lives. … It’s a piece of information that’s going to be useful for the whole of your life.”

As far as cancer patients are concerned, the project will compare genomes of tumors with those of healthy cells in order to determine mutations in the genes.

For patients of rare diseases considered ascribable to genetic mutations, their own genomes and those of their closest blood relatives will be compared.

Some 75,000 people will be involved as two genomes per cancer patient will be examined. The project will sequence 100,000 genomes by the end of 2017.

Taking breast cancer as an example, Chisholm said there are “at least seven different types” of the disease. Genomics is making it possible to find the “best method of treatment” for each type, he said.

In fact, the completion of the project will enhance the effectiveness of medical treatment by making a drug for each type available and enabling doctors to take into account patients’ separate constitutions for adverse effects.

In British society, there remain concerns about the government holding clinical and genomic information on individuals.

The project will collect data from people with their consent and ensure their anonymity. The leaking of data will be subject to a fine of up to £500,000.

But once digitized data are leaked, it will be impossible to recover.

“Lots of people are worried about insurance,” Vivienne Parry, head of engagement at Genomics England, said.

“If you’re on this project, you don’t have to disclose this information to your insurer,” she added.

The British life insurance industry has decided on a temporary policy to allow participants in the project not to disclose their genomic results to insurers.


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  • Liftstream

    This is a good development for rare disease patients, now and for the future. With so many of the 7000+ rare and ultra-rare conditions without any effective therapy, these sorts of programmes will hopefully bring a better understanding of the diseases.