Who would like to hear some really good news? Thought so. One of the promises of the molecular biology and genomics revolutions was that gene therapy – replacing defective, disease-causing genes with functioning ones, or otherwise treating these diseases by genetic means – would become a reality. Even, optimistically, something commonplace. Like so many things, however, it has proved more complicated than hoped, and those longed-for treatments elusive. There has never been a therapy of any kind that alters the disease progress of a neurodegenerative disease – until now. Continue reading
After my somewhat depressing previous post, I decided to comment on something a little more optimistic this time around, namely the success in getting treatments for some of world’s most underfunded diseases afflicting the world’s poorest people. And at a knockdown price, too… Continue reading
Back in my childhood when I first got into science fiction, I read all those classics, from early romantic science fiction like Jules Verne into the “golden age” of Asimov, Clarke and beyond. Ah, all those wonderful dreams of perfect societies, robots and spaceships! Except that the overwhelming majority of those perfect societies bore a striking resemblance to a certain ideal of 1950s America, where women were love interests/to be rescued/in the kitchen and people of colour were…er, nowhere to be seen, actually. Now that we’re in the timeline of the future that a lot of those books imagined, it’s refreshing that the science fiction is a lot more reflective of the wide variety of human experience that exists. I’d like to say that societies have progressed along with the technology, and, very unevenly, they have. A bit. And yet somehow it’s still really disappointing to me when I read something about personalised medicine, and that something is: it’s heavily biased towards white people. Continue reading
There is increasing concern over the rise in antibiotic resistance, with many infections now becoming resistant not just to commonly used, long-established antibiotics like penicillin, but to last-resort newer antibiotics like vancomycin. The search for new antibiotics is becoming increasingly urgent – and it seems that some are lurking in surprising places. Continue reading
There’s been a rush of new papers out lately which are starting to explain how Zika virus causes fetal damage. Understandably, since the suspicion of a link between Zika and microcephaly (an abnormally small head, associated with neurological defects) in humans was raised, there’s been an intensive research effort directed at uncovering the causality of this process, but I’m still impressed at the speed at which scientists are gaining answers. It was only last month, after all, that the CDC declared that there was a “causal link” between Zika and microcephaly. Continue reading
Following on from my post on the new treatment for ALL, I thought I’d go into cancer in general a bit more. In this first part of a double post, I’ll briefly go into what cancer is and the principles of the main types of current treatments. In the second part, I’ll consider some of the more futuristic cancer treatments that are starting to enter the mainstream.
News recently came out that a baby girl has been successfully treated for a particularly aggressive form of acute lymphoblasic leukaemia (ALL) using a form of gene editing. This is only the second time that gene editing has been used in people. The first involved modifying T-cells in HIV sufferers to make them more resistant to the virus, however, which was a far lower risk strategy as these people were not at imminent risk of dying.
ALL is a cancer of one of the two types of blood cell; the “white” ones, called lymphocytes, which fight infection. They are all produced in the bone marrow; a source of those famous stem cells: these are progenitor type cells that have the potential to multiply themselves (self-renewing) and for their offspring to differentiate into more than one type of cell. In the case of ALL, the stem cells for the white blood cells start multiplying uncontrollably, releasing lots of immature “blast” cells into the bloodstream. This reduces the number of red blood cells needed to carry oxygen, and also the number of mature white blood cells, so the body’s ability to fight infection is actually reduced. Treatment usually involves a combination of radiotherapy and chemotherapy to kill the cancerous cells (these techniques kill rapidly dividing cells – a hallmark of cancer cells and the major way treatments have traditionally targetted cancer cells – I will probably provide an overview of the principles of cancer and methods used to treat it in a later post; in the meantime, here is a useful link)
Essentially, what the researchers did was to take a type of immune cells (T-cell lymphocytes) and genetically engineer them using TALEN® proteins, which act as so-called “molecular scissors”; these cut double-stranded DNA and use the cell’s own repair mechanisms to join the gap, with your gene of choice inserted. In this case, an extra gene for a receptor called CAR19 was added. A receptor, incidentally, does exactly what it says on the tin; they are proteins that sit on the outside of cells and receive proteins that act as signals. In this case the signal was in the form of another protein, called CD19, that the ALL cancer cells have on their surfaces. The T-cells (called UCART19 cells) are then programmed to seek out and destroy the cancer cells. So far, so good, and there are several human trials underway for this. But there was one major snag – ordinarily, the T-cells to be engineered are harvested from the patient’s body, engineered, and put back, but in this case the patient was too small and ill to have enough to modify. What about using T-cells from a donor then? Great, except that these cells will be recognised as not belonging to the patient’s body, and destroyed by the immune system. In fact, leukaemia patients are given drugs that essentially destroy their immune system (as it is these cells that are cancerous) and so this shouldn’t be a problem – but one of the drugs also destroys donated T-cells. So, the team, led by Prof Qasim, did something rather clever, and used the TALENs to disable a second gene in the donor T-cells, which made them invisible to this drug.
One infusion (one!) of these cells essentially cured Layla of her cancer. Later on, she was given a full bone marrow transplant as her own immune system had been destroyed by all the cancer treatment. This means, incidentally, that none of the circulating donor UCART19 cells remain. And neither, all being well, do any cancerous cells at all.
This is more than just a neat solution to a problem specific to a particular patient: it is possible (and, indeed, is the aim of the Cellectis, the company that makes them) that T-cells could be engineered such that they are suitable for anybody, and could be an off-the-shelf treatment for these types of cancer, which holds great promise for future cancer treatments.
For more on the story, read GOSH’s press release here
For more on gene editing, Wikipedia has a link here