Gene Therapy Halts MS

26 September 2017

Interview with 

Brad Hoffman, University of Florida

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A potential new therapy to help the 2 million people around the world living with multiple sclerosis, or MS, has been announced by scientists in the US. MS is caused by a rogue population of immune cells attacking a substance in the brain and spinal cord called myelin. Myelin normally works like the insulator that you’d find around an electric cable; in the nervous system it shields and supports nerve fibres. But as the myelin becomes more damaged by the immune assault, nerve signals are no longer faithfully conveyed, and patients become progressively more disabled. Now researcher Brad Hoffman, from the University of Florida, has found a way to reprogramme the immune system to drive the creation of regulatory immune cells that can damp down the action of the rogue cells. Chris Smith heard how, in tests on mice, it stopped the disease in its tracks...

Brad - We do this by taking a harmless virus and engineering that virus to express the same marker that the rogue cells are going after. Doing this liver gene transfer, as we call it, induces a second type of cell called a regulatory t-cell. The regulatory cells can suppress the rogue cells that are causing the damage.

Chris - How are you actually doing these experiments? What are you doing to investigate this, because this is not in patient’s yet is it?

Brad - No, no, no; we’re not in patients as of yet. What we do is we have a mouse model that we can induce a multiple sclerosis-like disease that mimics many of the early stages that would be seen in human MS.

Chris - So talk me through what happens to these mice then and how you set the experiments up to prove that this virus you’ve engineered, which can drive the immune system to regulate itself better, what actually happens when you do this?

Brad - So basically what happens, when we induce disease in these mice, the mice that are not treated would in a process, in about two weeks, in which they become somewhat paralysed. If we give this treatment before we induce disease in the mice, we can completely prevent the disease from even starting. When we do this same technique trying to reverse the disease, about ten days to two weeks afterwards, the mice undergo a reversal of disease and they actually regain function in their extremities quite nicely and almost down to pre-disease levels.

Chris - And you can prove, can you, that the reason that’s happening is because you’ve now got this new population of immune master regulators that are suppressing what were previously these rogue cells attacking the nervous system?

Brad - Absolutely. When we do this technique we can identify the marker we have encoded into these cells that these cells are definitively targeting the same marker as the rogue cell so, when they encounter one another, they will suppress them.

Chris - Is this safe? Because, obviously, you’re putting a virus that shouldn’t be there into liver cells and making them express this nervous system protein that shouldn’t be there, and them making a whole population of immune cells spring up, which weren’t there; a lot of things changing. Are there side effects?

Brad - At this point, based on all the research we have going on, we do not see any side effects at this point. Liver function maintains the mice; are able to live long lives after we have done this if they’ve been treated. We don’t see, at least in the mouse model at this time, any adverse effects.

Chris - How far away do you think you are from being able to embark on a safe human clinical trial because, obviously, for the people who are afflicted with this disease, time is everything because it is a progressive condition?

Brad - We are probably several years away from being in the clinic. Our results are amazing results and we’re very optimistic of this being able to be translated into the clinic. The technique that we have used has already been tested in the clinic in some aspects, but not specifically. So, it’s going to take a little bit of time to kind of merge the technology that’s already in the clinic with the stuff that has to still be qualified for safety reasons to move it along to a human population.

Chris - Considering what might be achieved for people who already have disability, the immune attack on the nervous system often leaves, for want of a better phrase, scarring in the nervous system, which is why people do get progressively worse with MS. So, to what extent do you think you’ll be able to just stop the disease in it’s tracks and to what extent do you think you’ll be able to undo some of the pre-existing disability these people have got?

Brad - That’s, again, a great question. Based on all the research that we are presenting here that we have been working on, the technique that we’re using is definitely more geared towards somebody who has recently diagnosed that’s trying to stop the disease early in it’s path. The idea here is that if we can stop the disease from advancing that the patient would have a much longer quality of life over time. 

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