UCI professor leads fight against brain disorder

Deirdre Newman

UCI CAMPUS -- A ray of hope has emerged from a laboratory here for

those suffering from a debilitating brain disorder.

Professor Larry Marsh and his team in the biological science

department have discovered chemicals that may counteract the course of

Huntington’s disease. While it may be years before a treatment comes to

fruition, it is a positive step on the road toward treating progressive

neurological disorders.

“It’s exciting, but I have guarded optimism,” Marsh said. “Science is

like peeling back layers of an onion. Most of the time it’s just more

layers.”

Huntington’s disease is a genetic brain disorder that causes

uncontrolled movements, loss of intellectual capacity and severe

emotional disturbances, eventually resulting in death. There is no

treatment or cure available.

Newport Beach resident Jeannie Zetz knows what the effects of the

disease can be.

She lost her husband to Huntington’s disease, and her two children are

dealing with the crippling effects of the juvenile version of the disease

-- one is in a psychiatric hospital and another is in an assisted-living

facility.

“It’s really very sad because your hopes and dreams for your children

are cut short,” Zetz said.

Marsh’s research into Huntington’s disease started six years ago when

his team met with another UC Irvine genetics group that was trying to

identify the gene that caused Huntington’s disease. When they found it,

it proved similar to some molecules that Marsh was studying as part of

his cancer research.

He is publishing his findings today in the journal o7 Naturef7 .

Marsh thought it might be possible to engineer a fruit fly to have

Huntington’s disease-like symptoms, which would make the disease easier

to study. Since Huntington’s disease has debilitating psychological

effects, Marsh’s research was conducted in collaboration with professors

Leslie Thompson and Joan Steffan, professors of psychiatry and human

behavior.

His team hit the jackpot recently when it found one way the Huntington

gene works -- it throws off a class of biochemical pathways that are

delicately balanced.

The trick then was figuring out how to maintain the balance.

There are groups of proteins in the brain that regulate the activity

of genes, and they have opposing effects -- one group tries to turn them

off, and the other group tries to turn them on.

The Huntington’s disease gene was found to stifle the proteins trying

to turn the genes on, so Marsh and his team worked to restore the balance

by inhibiting the genes that try to turn the genes off.

These inhibitors are used in pharmaceuticals for cancer chemotherapy

that are now being tested for safety in the first phase of clinical

trials.

Marsh likens the painstaking research to trying to find a needle in a

haystack among many haystacks. But he remains optimistic that it will

ultimately generate treatment that can stop the symptoms of Huntington’s

disease before they start and also relieve the pain for those who are

already afflicted.

“What will be really exciting is if in five to 10 years, someone who

has Huntington’s disease is actually benefitingfrom this,” Marsh said.

FYI

The Huntington’s Disease Society of America will host its Celebration

of Hope fund-raising dinner Nov. 15 at the Hyatt Newporter.