3 UK Scientists Win Challenge Awards for Progressive MS Projects

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by Patricia Inacio, PhD |

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Research Challenge Awards

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Three scientists in the U.K. were given awards by the International Progressive MS Alliance that will support projects aiming to explore new approaches to treating progressive forms of multiple sclerosis (MS).

The three are among this year’s 19 winners of the alliance’s Research Challenge Awards, which totaled £1.2 million (about $1.7 million).

David Baker, PhD, a professor at the Queen Mary University of London, will use the funding to investigate ways to prevent nerve cells from becoming over-excited, meaning when they generate electrical signals more readily than is normal.

Higher levels of excitation lead to nerve cell exhaustion and premature death, a phenomenon that fuels the progression of diseases like MS. The researchers developed a lab-made chemical that limits the amount of excitatory signals in neurons. The chemical, designed to mimic a natural molecule found in our bodies, has the potential to halt this neural overexcitation and, consequently, nerve cell’s death.

“We’ve developed a chemical that we believe can help calm over-excited cells and protect them from exhaustion. Based on a chemical our bodies make naturally, it can enhance a gate-like mechanism, which allows certain charged particles to exit the nerve cells. This prevents the build-up of excitability which can be dangerous and lead to nerve cell death,” Baker said in a press release.

The researchers will test the chemical’s potential to protect nerve cells in MS, and watch for possible side effects.

Don Mahad, PhD, with the University of Edinburgh will expand on previous research showing that the loss of myelin that surrounds nerve fibers leads to a shortage of mitochondria, the cells’ powerhouses. As a result, nerve cells become depleted of the energy they need to work as intended.

Mahad and his team tested the potential of pioglitazone, a type 2 diabetes medicine, to raise mitochondrial levels in mice with defective energy production. Pioglitazone significantly increased the mitochondrial content in nerve fibers and protected nerve cells from death.

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“Last year we found that our nerves have a natural protective response when myelin, the coating that protects them, gets damaged in MS. And in animal studies we were able to enhance that response with a drug that’s already available [pioglitazone],” Mahad said.

With the new funding, the scientists will test whether the neuroprotective effects of pioglitazone are also observed in people with MS. Moreover, they will investigate further protective responses by nerve cells and whether they can enhance these natural protection mechanisms.

“We’re now able to take our findings forward to see if what we’ve found in mice is also true in brain tissue from people with MS. We also want to find out if nerve cells have other natural protective responses, and how we might help these processes along,” Mahad added.

Ken Smith, PhD at University College London will use the award to help in work aiming to pinpoint when damage done to nerve cells causes their death in progressive MS.

Specifically, the project will focus on the role of hypoxia (low oxygen levels) and whether targeting an oxygen shortage may prevent disease progression.

Each of the awardees will receive up to £65,000 ($89,295) for one year. The winning projects were selected by an international panel of MS experts and people affected by the disease.

Caroline Sincock, diagnosed in 1990 and a member of the selection committee, said: “I joined the Alliance because it brings together world-class expertise in a way that is completely unprecedented. MS organisations and researchers from around the world have come together to finally stop this condition, and the combined knowledge and reach is just extraordinary.”

“More than 130,000 people in the UK and 2.8 million worldwide live with MS. Thanks to research, we already have over a dozen licensed treatments for people with the relapsing form of MS, and some emerging for early active progressive MS. But too many people still don’t have any treatment to help them,” said Clare Walton, head of research at the U.K.’s MS Society.

“We believe we can stop MS. And by finding out what drives MS progression, these projects will bring us one step closer to finding treatments for everyone,” she added.

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