Photo: James Duncan Davidson
Regenerating hope: TEDGlobal 2013 with Siddharthan Chandran
Professor Siddharthan Chandran works in the emerging discipline of Regenerative Neurology.
His research combines laboratory and clinical activity that includes human stem cells and specialist clinics (multiple sclerosis and motor neurone disease) to both study disease as well as undertake early-phase clinical trials.
The ultimate aim of our research is to develop novel regenerative therapies for neurodegenerative disease through linked clinical research and laboratory studies that include human stem cells.
The Centre for Clinical Brain Sciences (CCBS) was established in 2004.
Edinburgh
Live from TEDGlobal 2013
Regenerating hope:
Siddharthan Chandran
Posted by: Karen Eng
June 12, 2013
Photo: James Duncan Davidson
Regenerative neurologist Siddharthan Chandran
asks whether we can repair the damaged brain.
Here’s the problem:
Humanity is facing an epidemic of fast-progressing, devastating
neurological disease such as Alzheimer’s, motor neuron disease,
Parkinson’s, multiple sclerosis
and Huntington’s.
Collectively, this is one of the biggest public
health threats of our time.
Over 35 million people are affected, and the
global annual cost is $700 billion and rising — greater than 1% of
global GDP.
Chandran shows two clips of one of his patients, John, who, speaking
through a respirator, explains that difficulty breathing in 2011 led to
the diagnosis of motor neuron disease. In the second video, 18 months
later, he explains that weakness in his legs means he now often uses a wheelchair,
illustrating not only the devastating consequences but the shocking
pace of the disease — a fit adult man rendered chair and respirator
dependent in 18 months.
How does it happen?
Chandran explains that the brain is “terribly
simple,” made up of four kinds of cells — some nerve cells and some
insulating, or myelin-producing cells.
“When they work together,” says Chandran,
“they create an extraordinary symphony of electrical activity” that
allows us to feel and emote.
But each of these cells can “go rogue or
die,” resulting in damaged wiring and disrupted connections, damage that
ultimately manifests in disease.
Chandran believes that hope lies in a new discovery — that
the brain
can spontaneously repair itself, an important fact that challenges old
medical orthodoxy. So it can, but it just doesn’t do it well enough to
overcome disease.
He shows an image of a brain affected by MS, where
damaged cells on the brain are being spontaneously repaired — not by
doctors, he says, but in spite of them, because stem cells endogenous in the brain are allowing new myelin to be laid down over the damaged nerves.
Photo: James Duncan Davidson
He asks why, if we’ve known this for a long time — and we have — are
there no treatments? Because drug development is expensive and
time-consuming and risky. The odds of isolating a treatment are 10,000
to 1, costing 15 years and $1 billion — and even then there’s no
guarantee.
Can we shorten the odds? Yes we can, says Chandran, but we have to
consider the point of failure. The problem, he says, is that traditional
development requires isolating five compounds from 10,000, which are
then sent to clinical trials,
which are first done on animals. Why not use stem cells to bypass
animal trials?
After all, he says, quoting Alexander Pope, “The proper
study of Mankind is Man.”
We can now do this thanks to stem cells. Stem
cells can do two things: they can self-renew, and they can specialize
– they can give rise to any other cell, whether a motor nerve cell, a
skin cell, a liver cell, and so on.
Over the last few decades, but especially in the past 10 to 15 years,
major developments are allowing us to harness this ability. Dolly the
sheep was the first example of an animal cloned from an adult cell.
Then, in 2006, Shinya Yamanaka made an even bigger breakthrough, showing
that four ingredients could effectively convert any adult cell into a
master stem cell, effectively generating a personalized tissue-repair
kit of pluripotent cells.
How can easily-pluripotent stem cells
be useful for repairing the damaged brain? There are two ways. First,
we can discover new drugs in a dish. Take a patient skin sample,
reprogram it to make pluripotent stem cells and drive it to make a motor
nerve cell, and ask how it compares to a healthy counterpart cell from a
relative with a close genetic match. Comparing the health of the cells,
one could observe, for example, that the unhealthy cell is 2.5 more
likely to die than the healthy counterpart — a perfect assay for drug
discovery. Using a high-throughput screening system, you can seek the
drug that might be the most effective, and take it directly to human
trial, bypassing animal testing. We can also use stem cells to repair
damage, whether by activating those already in our brains to respond
appropriately to damage, or by transplanting stem cells directly to
replace dead or dying cells in the brain.
Photo: James Duncan Davidson
To close, Chandran cites an experiment investigating whether the stem cells
grown from patients’ bone marrow could promote repair of damaged optic
nerves in patients with MS. The study measured the size of the optic
nerve before and after the stem cell injection. The optic nerve was
measured after periodic injections, and Chandran found that optic nerves
that had previously been shrinking began to grow. Chandran believes
that the treatment was promoting the endogenous stem cells to “wake up”
and make new myelin.
With this, the talk ends on an optimistic note. Chandran asked his
patient, John, his hope for the future: “I hope that you can come up
with a cure so that people like me can live a normal life.”
Chandran makes an exciting case that we’ll be able to repair the damaged brain sooner than we think.
Tags for this story:
cell regenerationLive from TEDGlobal 2013motor neuron diseasemultiple sclerosisregenerative neurologistSiddharthan Chandranstem cells
commented on Jun 12 2013