Archive for the ‘CELLS’ Category

IVF baby born using the latest revolutionary genetic-screening process

Saturday, May 28th, 2016

Next-generation sequencing could enable IVF clinics to determine the chances of diseases developing in children

David-Levy-and-Marybeth-S-010 with dna selection image

Baby Connor Levy with his parents David Levy and Marybeth Scheidts

The first IVF baby to be screened using a procedure that can read every letter of the human genome has been born in the US.

Connor Levy was born on 18 May after a Philadelphia couple had cells from their IVF embryos sent to specialists in Oxford, who checked them for genetic abnormalities. The process helped doctors at the couple’s fertility clinic in the US select embryos with the right number of chromosomes. These have a much higher chance of leading to a healthy baby.

The birth demonstrates how next-generation sequencing (NGS), which was developed to read whole genomes quickly and cheaply, is poised to transform the selection of embryos in IVF clinics. Though scientists only looked at chromosomes – the structures that hold genes – on this occasion, the falling cost of whole genome sequencing means doctors could soon read all the DNA of IVF embryos before choosing which to implant in the mother.

If doctors had a readout of an embryo’s whole genome, they could judge the chances of the child developing certain diseases, such as cancer, heart disease or Alzheimer’s.

Marybeth Scheidts, 36, and David Levy, 41, had tried another fertility treatment, called intrauterine insemination (IUI), three times without success before they signed up for IVF at Main Line Fertility clinic in Pennsylvania.

As part of an international study with Dagan Wells, a fertility specialist at Oxford University, the couple were offered NGS to check their IVF embryos for abnormal chromosomes. Abnormal chromosomes account for half of all miscarriages.

The chances of an embryo having the wrong number of chromosomes rises with the mother’s age, and potentially with the father’s. For women in their 20s, one in 10 embryos may have the wrong number of chromosomes, but for women in their 40s, more than 75% can be faulty.

Most of the time, embryos with abnormal chromosomes fail to implant in the womb. Those that do are usually miscarried. The portion that survive to full term are born with genetic disorders, such as Down’s syndrome and Turner syndrome.

After standard treatment at the US clinic, the couple had 13 IVF embryos to choose from. The doctors cultured the embryos for five days, took a few cells from each and sent them to Wells in Oxford for genetic screening. Tests showed that while most of the embryos looked healthy, only three had the right number of chromosomes.

“It can’t make embryos better than they were in the beginning, but it can guide us to the best ones,” said Wells.

Based on the screening results, the US doctors transferred one of the healthy embryos into Scheidts and left the rest in cold storage. The single embryo implanted, and nine months later Connor was born. Details of the study will be given at the European Society of Human Reproduction and Embryology (Eshre) meeting in London on Monday.

“I think it saved us a lot of heartache,” Scheidts told the Guardian. “My insurance covered me for three cycles of IVF. We might have gone through all three without the doctors picking the right embryos. I would not have a baby now.”

A second baby who had the same genetic screening is due to be born next month, after a US couple had IVF at New York University fertility centre.

Doctors can already screen embryos for abnormal chromosomes using a technique called Array CGH, but the procedure adds more than £2,000 to the cost of IVF. Wells said NGS could bring the cost down by a third. To check the number of chromosomes is much simpler than reading all of the DNA accurately.

“It is hard to overstate how revolutionary this is,” said Michael Glassner, who treated the couple at the Main Line Fertility clinic. “This increases pregnancy rates by 50% across the board and reduces miscarriages by a similar margin. It will be much less expensive. In five years, this will be state of the art and everyone who comes for IVF will have it.”

In Britain, doctors are banned from selecting embryos for anything other than the most serious medical reasons. But as scientists learn more about genetic causes of disease, the urge to choose embryos to avoid cancer and other diseases later in life will intensify.

“You can start to have a very scary picture painted if you talk about height and hair colour and so on,” said Glassner. “We have to make sure this is used judiciously.”

The prospect of “designer babies” is remote for now, even if it were made legal. IVF produces only a dozen or so embryos at best, so the odds that one has all the traits a couple desires are very low. “IVF is still expensive and uncomfortable with no guarantee of a baby at the end. I can’t imagine many people wanting to go through the strains of IVF for something trivial,” said Wells.

The Oxford team now plans a large trial of the screening procedure to assess how much it boosts pregnancy rates, and which age groups it benefits the most.

Scheidts still has two screened embryos in cold storage, but has not yet decided whether to use them. “We haven’t even thought about that. We’ll see how the first year goes.”


Henry Sapiecha

Designer immune cells used to treat ‘incurable’ leukaemia case

Friday, November 6th, 2015

lab testing image

A treatment that uses “molecular scissors” to edit genes has been used for the first time by UK medics successfully to treat a one-year-old girl with an “incurable” form of leukaemia.

The case at Great Ormond Street Hospital in London involved the creation of “designer immune cells” programmed to hunt and kill the disease. The girl, called Layla, is now cancer free and doing well, according to the hospital.

The breakthrough will add to excitement over the fast-emerging field of gene-editing — a type of genetic engineering in which DNA is inserted, replaced or removed from genes to fix faults or fight disease.

Gene-editing has caused controversy because of its potential to be used in ethically dubious ways, such as the creation of “designer babies”. However, the London success helps show why many scientists are so enthusiastic about the technology.

The so-called UCART19 cells used at Great Ormond Street had shown promise in animals but had never been used in humans before they were administered as a last-ditch attempt to save Layla after other drugs failed.

“The approach was looking incredibly successful in laboratory studies and so when I heard there were no options left for treating this child’s disease, I thought, ‘why don’t we use the new UCART19 cells?’” said Waseem Qasim, professor of cell and gene therapy at University College London’s Institute of Child Health.

The treatment, developed by a French biotech company called Cellectis, consisted of 1ml of UCART19 cells injected into Layla’s bloodstream. After several weeks it was clear the leukaemia cells were disappearing.

“We didn’t know if or when it would work and so we were over the moon when it did,” said Paul Veys, director of bone marrow transplant at Great Ormond Street. “Her leukaemia was so aggressive that such a response is almost a miracle.”

We didn’t know if or when it would work and so we were over the moon when it did. Her leukaemia was so aggressive that such a response is almost a miracle

– Professor Paul Veys

The treatment is similar to cancer therapies in development using modified T-cells from companies including Novartis of Switzerland and Juno and Kite of the US. However, whereas others use cells extracted from the patient’s own blood, UCART19 cells come from healthy donors.

This overcomes the problem of many leukaemia patients not having enough healthy T-cells — a type of white blood cell that fights off disease — to be harvested after chemotherapy.

A further possible advantage is that donor cells can be mass produced for use in any patient, making them potentially more affordable than rival treatments that must be personalised for each individual. High costs are viewed as one of the biggest drawbacks of the so-called CAR-T therapies under development by Novartis, Juno and Kite.

Matt Kaiser, head of research at Bloodwise, a blood cancer charity, said the possibility of UCART19 cells providing an “off-the-shelf” treatment could be an important advance but cautioned that larger clinical trials were needed to prove it was safe and works.

“The concept of training immune cells to specifically recognise and hunt out leukaemia cells is very exciting and in theory could provide a lifetime cure for these children,” he said.

The promising signs for UCART19 is good news for Servier, the larger French drugmaker that has rights to commercialise the product, and for Pfizer, which has a partnership with Cellectis on similar experimental therapies.


Henry Sapiecha

Molecular ‘eat now’ signal makes well cells devour dying neighbors cancer cells

Thursday, July 17th, 2014

A team of researchers has devised a Pac-Man-style power pellet that gets normally mild-mannered cells to gobble up their undesirable neighbors. The development may point the way to therapies that enlist patients’ own cells to better fend off infection and even cancer, the researchers say.

A healthy cell (green) that has recognized and engulfed dying cells (purple) is shown. Credit Toru Komatsu University of Tokyo image

A description of the work will be published July 15 in the journal Science Signaling.

“Our goal is to build artificial cells programmed to eat up dangerous junk in the body, which could be anything from bacteria to the amyloid-beta plaques that cause Alzheimer’s to the body’s own rogue cancer cells,” says Takanari Inoue, Ph.D., an associate professor of cell biology in the Johns Hopkins University School of Medicine’s Institute for Basic Biomedical Sciences, who led the study. “By figuring out how to get normally inert cells to recognize and engulf dying cells, we’ve taken an important step in that direction.”

Identifying and devouring dying cells and other “junk” is usually the job of white blood cells called macrophages and neutrophils, which also go after bacteria and other invaders in a process called phagocytosis. For the new experiments, Inoue teamed up with researchers at the University of Tokyo to strip down phagocytosis, figuring out the minimum tools one cell needs to eat another one.

They started not with macrophages, but with a type of laboratory-grown human cells known as HeLa, which normally can’t perform phagocytosis. Their first task was to induce the HeLa cells to attach to nearby dying cells by getting the right “receptors” to the HeLa cells’ surface. The researchers knew that part of a receptor protein called MFG-E8 would recognize and stick to a distress signal on the surface of dying cells, and coaxing the HeLa cells to make the protein fragment was straightforward. To get the fragment, termed C2, onto the outside of the cells, the team found a way to stick it to another protein that was bound for the cell’s surface, thus taking advantage of the cell’s own transportation system. “We put C2 on the same bus as the membrane protein,” Inoue says.

As a result, up to six dying cells stuck to each HeLa cell. The bad news was that though they were cozy, the HeLa cells weren’t actually eating the dying cells.

Fortunately, Inoue says, the team already had an idea about what to try next: Other research had shown that activating a gene called Rac would cause a cell to engulf beads stuck to its surface. Sure enough, HeLa cells with both surface C2 and activated Rac swallowed dying cells readily, the team found.

“We’ve shown it’s possible to endow ordinary cells with the power to do something unique: take on the role of a specialized macrophage,” Inoue says.

Inoue cautions that the investigators don’t believe the engulfed cells are being broken down. Getting the HeLa cells to finish the phagocytosis process will be one of the group’s next steps.

Henry Sapiecha