Recurring nightmare

Years later, some polio survivors suffer pain anew

Stories by Mark Sauer
STAFF WRITER

November 15, 2000

Researchers trying to learn
what causes breakdown in
body's recovery system

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A half century ago, parents and children lived in crippling fear of a crippling virus.

Polio.

The very name conjured heart-rending images of children in leg braces and iron lungs.

The disease usually struck in summer. Kids romping one day lay motionless the next in polio's fevered grip. In 1952 alone, 50,000 Americans were stricken; 12 percent of them died, thousands more were left paralyzed.

In one of medicine's greatest 20th-century triumphs, researcher Jonas Salk, then of the University of Michigan and later of La Jolla, developed an injectable killed-virus vaccine in 1955.

Six years later, Albert Sabin's live-virus vaccine improved on Salk's breakthrough, and by the mid-1960s polio was virtually eradicated in this country. To later generations of kids and parents, polio represented the past, not a plague.

But polio's reign of misery was not over.

In the late 1970s, some victims who had overcome the disease decades earlier through determined therapy began reporting pain in muscles and joints, severe fatigue and, ominously, muscle weakness and breathing problems.

Before long, the condition had a name: post-polio syndrome.

Though studies have identified more than 600,000 paralytic polio survivors in this country, no one knows how many have experienced post-polio-syndrome. Some research suggests the number may be as high as 40 percent, or about 250,000 Americans.

But diagnosis and effective treatment have proved elusive.

That could be changing.

At Salk's seaside institute in La Jolla, Sam Pfaff, a developmental neurobiologist, and his team of researchers probe chicken and mice embryos to determine the genetics of how motor neurons develop to connect the spinal cord to muscles.

At the UCLA School of Medicine, Dr. Susan Perlman works with patients suffering from post-polio syndrome to learn what therapies and medications work to quell the degeneration of their bodies.

For people such as San Diegan Mary Clare Schlesinger, who battles PPS every waking moment, Pfaff and Perlman and PPS researchers at other medical centers represent the kind of hope that Salk and Sabin delivered nearly 50 years ago.

"For the most part, the medical community and the public think polio is a disease of the past and are totally ignorant of PPS," said Schlesinger, a leading activist in San Diego post-polio support groups.

During the epidemics, the vast majority of people exposed to polio did not even know they were infected, Pfaff said; others became mildly ill. Some victims suffered temporary paralysis and recovered quickly; others were more severely paralyzed when muscles in legs, arms or those affecting breathing failed.

Many of these people recovered fully. Others, including Mary Clare Schlesinger, never "made it back completely," as she put it.

Today, those newly diagnosed with post-polio syndrome usually go through the stages of grief: anger, denial and finally acceptance, Schlesinger said.

"You are grieving for your loss, but it's a continuous thing. It often depends on how PPS strikes. For some, it happens quickly; for others it's a slow, degenerative process.

"Some people hit a plateau for a couple of years then start getting worse again and the grieving comes right along with it."

Schlesinger describes her struggle with PPS as a waking nightmare.

It's like being "entangled in a mass of ropes at the bottom of a big box," she said. "I free myself from the ropes and start climbing; but every time I reach the top, I fall back down."

  

Atop the concrete research fortress Jonas Salk built on a La Jolla bluff, Sam Pfaff toils where the great polio slayer once worked himself.

He is a genetic detective trying to unravel the molecular mechanisms behind the creation and development of neurons and how neuronal signals move through the body.

Pfaff hopes his staff's research into how the brain, spinal cord and muscles are wired together may one day benefit hundreds of thousands of people in this country.

But unlike Jonas Salk, Pfaff said, "our research is not disease specific." In addition to PPS, knowledge of the workings of neurons could benefit victims of Lou Gehrig's disease, spinal-cord injuries, Parkinson's disease, multiple sclerosis and other neuromuscular conditions.

The mystery centers on motor neurons, the nerves that control muscles. It is these neurons that the polio virus attacked, Pfaff said.

Motor neurons in the spinal cord are connected to muscles through long tentacles called axons. Signals from the motor neurons travel along the axon to the muscles, signaling them to contract.

In typical cases, the polio virus infects 95 percent of motor neurons in the spinal cord along with many nerve cells in the brain. The cells either overcome the virus, or die.

Motor neurons that survive form new axon sprouts, the body's way of keeping as many muscle cells alive and functioning as possible, Pfaff said. "An individual may lose as many as half his motor neurons yet still retain normal muscle strength," he said.

"The body works hard to compensate for the loss by sprouting new axons that branch onto muscles and drive contractions. That's why many youngsters who once needed iron lungs recovered to breathe on their own."

With the additional axon sprouts, a motor neuron that once stimulated 1,000 muscle cells might now control 5,000 or 10,000 cells. These new powerhouse neurons allowed polio victims, in many instances, to overcome paralysis and regain full or nearly full use of their muscles.

But what happens over time to undermine this process?

Scientists aren't certain.

The leading hypothesis in post-polio syndrome is that overuse of remaining motor neurons causes a slow degeneration of the axon sprouts that innervate the muscle cells.

But not nearly enough is known about the workings of motor neurons in the spinal cord and brain to determine where the breakdown is occurring.

That's where Pfaff and his researchers come in.

"I use the analogy of a car. If you were to stand on the assembly line in Detroit and see exactly how a car is put together piece by piece, you could then figure out what's going on when it breaks down," he said.

"We're attempting to look at the genetic assembly line. We're not so concerned with the cause of the breakdown in motor neurons, but with how it can be fixed."

Pfaff, 38, uses mice and chick embryos to discover how genetics govern the extraordinarily complex development and function of motor neurons.

"Early on, all cells in the spinal cord start out from pretty much the same place. In fetal development, they learn who they are. The important question is what causes one to become a motor neuron and another to become a different kind of neuron?" Pfaff said.

Finding the answer could take awhile.

Pfaff and his research staff, for example, were surprised to discover that several genes active in the pancreas are essential to the generation of motor neurons -- a fact that strikes them as completely illogical.

In their embryo research, Pfaff said his staff has centered on which genes need to be switched on or off at a precise time for motor neurons to develop normally.

They focused, for instance, on the gene Hb9 (for homeobox 9), which has been linked to a rare birth defect causing malformations in the pelvic and sacral areas. To determine how Hb9 affects motor-neuron development, the Salk researchers engineered "knockout mice" in which the gene was missing.

The mutated mice embryos developed motor neurons but did not survive birth because they couldn't breathe properly. The lesson: Hb9 has to do with guiding axons to the right muscles that control breathing.

About 25 genes involved in the development of neurons have been identified so far, though more needs to be learned about their precise functions, Pfaff said.

"We're trying to tease out the tricks nature is using. And we're starting to figure it out."

Copyright 2000 Union-Tribune Publishing Co.