Biogel can heal brain after stroke

18 December 2018

Interview with 

Tom Carmichael, University of California, Los Angeles & Kativa Basi

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Having a stroke can have devastating effects on your life, especially as damaged parts of the brain can't recover after the fact. Or can they? Georgia Mills spoke to neurologist Tom Carmichael University of California, Los Angeles, about research he’s pursuing to regrow brain tissue after a stroke, after hearing from Kavita Basi, who survived a brain haemorrhage.

Kavita - In 2015, when I was 38 years old, I was taken into a A&E with a life threatening illness: A subarachnoid brain haemorrhage. Prior to this, I was leading a happy, healthy lifestyle. I just didn't expect that something like this would happen to me. The night it happened, I had come home from work a little earlier with a headache and watched some TV, and I woke up then approximately 11 p.m. screaming with huge pain, as if a sledgehammer had hit the back of my skull and I had a seizure then, and collapsed. I was then treated at the Salford Royal Hospital in Manchester with various operations over the next few weeks. My life now is adapting to this new me. I have trouble with short term memory loss, severe headaches, difficulties with certain noises, claustrophobic, high anxiety, and also a personality shift.

I now have very straightforward black-and-white thinking and this is difficult for people who know me to understand.

Chris - Kavita Basi, who recently published a book on her experiences called Room 23; Surviving a Brain Haemorrhage.

Georgia - Having a stroke can have a devastating effect on your life and recovery is especially difficult because the damaged areas of the brain are permanently dead, or are they? I spoke to neurologist Tom Carmichael of the University of California, Los Angeles about research he's pursuing to regrow brain tissue after a stroke.

Tom - The key cell types in the brain, the neurons, that send the signals really are fixed after a certain age in humans. Somewhere between 2 and 5 years old, we don't get anymore brain cells and so we can't as a result, regenerate new brain cells themselves in large quantities. And so when there is an area of dead brain you can't regrow into that area normally. From the brain next to it because the brain cells themselves, the neurons, are what we call in in the scientific field, postmitotic. They can't divide and form substantial quantities of new cells.

Georgia - Would you call this scarring then, these dead cells?

Tom - Yes, what happens is the area dies and then some of these cells called glia, proliferate, and wall off the area of damage, and they participate along with other cells in the formation of a scar that helps contain the damage, but may also have a second effect of limiting some of the repair in recovery.

Georgia - How would that reflect in, sort of, the treatments you can give people?

Tom - Currently, as many will know, there are no medical therapies for recovery in stroke. The treatment is activity based; physical therapy, occupational therapy, or speech therapy. These are very limited in their efficacy. And so there are no therapies that stimulate recovery in stroke. And what we've been focusing on is the science of what the cells do after stroke, and how we might develop medical therapies that enhance that recovery.

Georgia - Right. Yeah. How is your lab investigating this?

Tom - We're very interested in what the brain starts to do, and then gets stuck and doesn't progress fully. So we've been investigating the molecules that stimulate brain cells to form new connections, or the molecules that stimulate blood vessels to grow and branch out in the tissue adjacent to stroke. And our reasoning is if we can understand those molecules we might understand why they don't produce a more full recovery, and then develop drugs that boost those molecular systems and boost recovery.

Georgia - How are you testing out the properties of these?

Tom - The first test is just a discovery process to get an idea or a hypothesis on a specific molecular pathway or molecule that might have a role in recovery. So in the example I just cited, we might identify a molecular memory system and say, we think this might have a role in stroke. And so the first test is a discovery test just to see in an animal model of stroke, like in a laboratory mouse, does this molecule enhance recovery.

Georgia - How have you put in the molecule to the mouse and what did you find?

Tom - There's a couple of ways we've done that. The most translationally relevant way is to deliver a drug that would interact with these systems, a candidate drug. We've partnered with pharmaceutical companies who have early stage discoveries that we might test. And we've also developed some of our own. And you can deliver that systemically to a mouse just like you would do a human. There are other more specialised ways. One exciting way is to develop new biomaterials that might enhance recovery and stroke. I mentioned that the stroke causes a cavity. That's a space in the brain that we might fill with a biomaterial, that could release a drug or that could have a molecule in it that promotes recovery. So delivery just like we would in a human systemically, or local delivery using new technologies like biomaterials.

Georgia - Wow. So like you'd put a plaster on a wound on your skin you, sort of, put the bio-plaster inside the damaged part of the brain?

Tom - Exactly.

Georgia - What happens then, when you tried this in mice?

Tom - Lots of times we have failure and that should be expected. It's discovery science and if you're not making mistakes you're not casting your net broadly enough, but in several instances we've had really substantial success and some of these have led to clinical trials, and some of these have really defined a new direction that we might then, in a sort of, iterative way, tune towards producing a human therapy.

Georgia - And when you say success do you mean parts of the brain that have died coming back online?

Tom - That's a very good question. There's probably two ways I might answer that. The first is to directly answer it, and that is yes we've developed what's called a biopolymer hydrogel, basically a jello-like material that's made of naturally occurring molecules in the body, and that can promote regeneration of new tissue after stroke. So in published accounts we've shown that it can cause axons, which are the connections of neurons, and blood vessels to grow into the damaged cavity and form essentially, new brain tissue that enhances recovery. And then a second answer to your question is what does it look like when the tissue recovers. Growing new brain with a bioengineered material is really a heroic feat that took years of work. Another approach is to simply enhance recovery of the existing but partially damaged circuits next to the cavity, and so recovery there might look like a circuit that originally say, was involved in moving the leg can now move the leg and the arm.

Georgia - Wow that's amazing. Do you know how long before maybe you start to see human trials?

Tom - There are various efforts that could go, in five years into clinical trial. The roadmap is well established for those. For others it may take seven to ten years. And that's particularly true for the more experimental therapies because there are a number of daunting translational problems. For example scaling up. Most of the processes that work in mice or in laboratory rats produce small quantities and to get into a possible human application you have to scale up in a very pure way to a large quantity and that's demanding and so there's a lot of, less interesting from a scientific perspective, problems that have to be solved to move many of these biomaterials efforts forward.

If you are in the UK and have been affected by stroke, you can get in touch with Different Strokes, a charity that supports younger stroke survivors at www.differentstrokes.co.uk

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