NYT Article on stuttering / IMVA - The Terror of Pediatric Medicine - September 12, 2006

[Guest guest]

> NYT today has an article about using anti-psychotics to " treat "

> stuttering. KS

>

Interesting statistics mentioned in the NYT article:

" Still, much remains to be learned about the causes of stuttering and

how to treat it. It is estimated that about 1 percent of the population

worldwide stutters, though that figure may be high. Men who stutter

outnumber women by a ratio of about 4 to 1, for reasons not known. "

To Fight Stuttering, Doctors Look at the Brain

Images by Luc de Ni

PET scans show, left to right, a nonstutterer, and then a stutterer

before, three weeks after and one year after behavioral treatment and

practice. Eventually, brain activity decreases, as speech becomes more

automatic.

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By ANDREW POLLACK

Published: September 12, 2006

As a child who stuttered badly, Gerald Maguire learned the tricks of

coping.

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For Some, Acceptance or Support Is Answer (September 12, 2006)

Images by Luc de Ni

M.R.I. images show the auditory cortex more active in a nonstutterer,

left, than a stutterer.

Diani for The New York Times

Dr. Gerald Maguire, a student of stuttering.

When called upon in class, he would sometimes answer in the voice of

Elmer Fudd or Duck because he didn’t stutter when imitating

someone. He found easier-to-say synonyms for words that stymied him.

And he almost never made phone calls because he stumbled over a phrase

for which there was no substitute: his own name.

Now Dr. Maguire, a psychiatrist at the University of California,

Irvine, wants to cure the ailment that afflicts him and an estimated

three million Americans. He is searching for a drug to treat

stuttering, organizing clinical trials and even testing treatments on

himself.

He could be getting closer. In May, Indevus Pharmaceuticals announced

what it called encouraging results from the largest clinical trial ever

of a drug for stuttering. Even larger trials are still needed, which

could take two or three years. But if they succeed, the drug,

pagoclone, could become the first medical treatment approved for

stuttering.

That is just part of a transformation of stuttering — in the medical

view — from what was once widely considered a nervous or emotional

condition to a neurological one that is at least partly genetic. Using

brain scans, DNA studies and other modern techniques, scientists — many

of whom stutter themselves — are slowly shedding light on a condition

that has flustered its victims as far back as Moses, who some scholars

believe was a stutterer because he told the Lord that he was “slow of

speech and of a slow tongue” and had his brother speak for him.

“This is a total paradigm shift in the last 10 years,” said Dr.

Maguire, who helped design the Indevus trial and was an investigator in

it. “When I was in medical school, I learned nothing about stuttering.”

Still, much remains to be learned about the causes of stuttering and

how to treat it. It is estimated that about 1 percent of the population

worldwide stutters, though that figure may be high. Men who stutter

outnumber women by a ratio of about 4 to 1, for reasons not known.

In most cases, stuttering begins between ages 2 and 6, when a child is

just learning to speak. But three quarters of such children will stop

stuttering within a few years without any intervention, said Ehud

Yairi, emeritus professor of speech and hearing science at the

University of Illinois, who stutters himself. Other children benefit

from speech therapy.

Those who stutter say the condition — marked by repetitions of

syllables, long silences and the contortion of the face as a person

seems to try to force the words out — can exact a terrible emotional

toll. Many talk of jobs or promotions not received, of relationships

broken or not pursued. Some structure their entire lives to avoid

having to speak unnecessarily or to avoid being teased.

“Stuttering is one of the last diseases it’s still O.K. to make fun

of,” said Ernie Canadeo, an advertising executive from Oyster Bay,

N.Y., who stutters.

Alan Rabinowitz, a noted wildlife conservationist, has told of how when

called upon by a teacher in elementary school, he once avoided

answering by stabbing his hand with a pencil so he would be taken to

the hospital.

Still, many people overcome — if not totally cure — their stuttering,

either through therapy or just the passage of time. Winston Churchill

stuttered. So did Marilyn Monroe. Others who have coped with the

problem include the author Updike, Senator ph R. Biden Jr. of

Delaware, the actor Earl , the newsman Stossel, the

singer Carly Simon and the sportscaster Bill Walton. Throughout

history, various theories have been advanced for stuttering, including

sexual fixations, emotional disorders, nervousness, and persistence

into adult life of infantile nursing activities, according to the book

“Knotted Tongues: Stuttering in History and the Quest for a Cure” by

Benson Bobrick (Simon & Schuster, 1995).

One of the more popular theories from a few decades ago was that

parents caused stuttering by reacting negatively to the repetitions

that normally occur when children first learn to talk.

But a consensus is growing that stuttering is a neurological condition,

though its exact nature is not clear. Emotional stress can make

stuttering worse, however.

Brain imaging studies have shown that the brains of people who stammer

behave differently from those of people who don’t when it comes to

processing speech.

Luc De Nil, chairman of the department of speech and language pathology

at the University of Toronto, said that in people who don’t stutter,

speech processing is largely handled in the brain’s left hemisphere.

With stutterers, there is an unusually large amount of activity in the

right hemisphere.

Dr. Maguire said studies that he and others had done also suggest there

is an excess of the neurotransmitter dopamine in the brains of those

who stutter.

Stuttering also appears to be at least partly genetic. About half of

the people who get treatment for stuttering have an immediate family

member who also stutters, said Dennis Drayna, a geneticist at the

National Institute on Deafness and Other Communication Disorders.

Scientists believe there are many genes that can contribute to

stuttering, each one perhaps having a small effect. That has made it

more difficult to find the genes.

But Dr. Drayna and his colleagues got a big break when a man from

Cameroon wrote to an online forum on stuttering a few years ago. The

man was part of a prominent family in which 48 of 106 adults stuttered,

suggesting that the gene responsible for the family’s stuttering was

inherited by changes in one gene.

Studying the DNA from that family, Dr. Drayna and his colleagues have

narrowed the search to a stretch of Chromosome 1 containing 50 to 60

genes. Another study using families from Pakistan with large numbers of

stutterers found a region on Chromosome 12, and that specific gene is

close to being identified, Dr. Drayna said. Other studies have found

other chromosomal regions.

If the cause of stuttering has baffled scientists, so has its

treatment. A 16th-century Italian physician prescribed nosedrops to

“dehumidify” the brain, according to Mr. Bobrick’s book. An American

Indian tribe made stutterers spit through a hole in a board to drive

the devil from their throats.

Most people who are treated for stuttering nowadays undergo various

types of speech therapy. Some therapies teach speech techniques, like

elongating vowels or speaking slowly. Others emphasize reducing the

anxiety and fear of speaking.

“Adults can be significantly helped,” said Ramig, a professor of

speech language pathology at the University of Colorado, who stutters.

“But it would be very unusual to see documented cases of adults who

stutter being cured.”

Some stutterers have been helped by devices. The best known is the

SpeechEasy, which fits in the ear like a hearing aid and feeds the

voice back to the speaker with a tiny delay and at a slightly different

pitch. This is said to simulate the choral effect, in which people

don’t stutter when speaking or singing in unison with others. The

device costs about $5,000, and 6,000 have been sold since 2001,

according to the manufacturer, the Janus Development Group of

Greenville, N.C.

Specialists say that the device helps some people but not others and

that the effects can wear off.

As for drugs, there have been some studies over the years using

medications developed to treat other conditions. Dr. Maguire ran small

trials of two schizophrenia drugs, Risperdal, from & ,

and Zyprexa, from Eli Lilly. Both drugs showed some effectiveness, but

neither company took the drug into larger trials.

That has frustrated Dr. Maguire, who said pharmaceutical companies

could be missing a big market. In the past, some critics have accused

pharmaceutical companies of taking conditions like anxiety or

inattentiveness, which the critics say are not clearly illnesses, and

turning them into medical problems so they could sell drugs. But

stuttering, Dr. Maguire said, is clear cut.

One obstacle is that stuttering has been primarily treated by speech

therapists, who can’t prescribe drugs and might object to the condition

being treated as a medical one. “There are many people who simply have

a bias against it and don’t think it’s a good idea,’’ said J.

Yaruss, a speech therapist at the University of Pittsburgh.

Another is that side effects might be worth risking for a serious

disease like schizophrenia but not for stuttering.

Zyprexa has been linked to weight gain and diabetes. Dr. Maguire

himself has taken Zyprexa for seven years and says it has greatly

helped his fluency. He has gained 20 pounds in that time but believes

he would have gained some of it anyway because he was approaching

middle age.

Pagoclone, the newest candidate, was initially tested as a treatment

for panic disorder and anxiety. Results were mixed, and Pfizer, which

had the rights to the drug, returned them to Indevus.

But in those trials a few people who stuttered said their speech

improved during the trial. So Indevus got a patent covering the use of

the drug for stuttering and began the clinical trial, in which 88

patients got the drug and 44 a placebo.

The participants were videotaped in conversation and reading, both

before starting on the drug or a placebo and four and eight weeks

afterward. Evaluators, blinded to whether the patient was on the drug

or the placebo when the video was made, counted the proportion of

syllables stuttered and the duration of the three longest stutters. In

a separate measure, clinicians evaluated the speech of their patients.

In most cases, those who got the drug did better than those who got the

placebo by a statistically significant amount. As evaluated by the

clinicians, 55 percent of those who got the drug improved after eight

weeks, compared with 36 percent on the placebo. The most common side

effects were headache and fatigue.

Still, until the results are published in a journal the company will

not reveal how big the improvement was for people, or whether it was

enough to make a real difference in their lives.

It’s also not quite clear how the drug is working, whether it is merely

reducing anxiety or has some other effect on speech. The drug activates

a receptor in the brain called GABA that is associated with a calming

effect.

Indevus has not said whether it will continue to pursue pagoclone for

stuttering because it is outside its focus of urology and gynecology.

It is also testing pagoclone as a treatment for premature ejaculation.

The company, under a previous name, Interneuron Pharmaceuticals,

developed Redux, a diet drug that became part of the fen-phen

combination. Wyeth, which sold the drug, withdrew it from the market

after it was linked to heart valve problems.

Byrne of Fountain Valley, Calif., who is taking pagoclone as

part of an extension of the clinical trial, said, “I definitely think

it’s helping me.” Another woman taking it said, “It’s left me feeling a

little bit more free, and I engaged in more speaking situations.”

Dr. Maguire is more enthusiastic. On a conference call for securities

analysts held by Indevus, he said some patients taking the drug had

finally gotten jobs they wanted or were able to approach others and go

out on a date. “It’s almost an awakening, people coming out of their

shells, so to speak.”

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On Sep 12, 2006, at 12:39 PM, krstagliano wrote: