Fibrodysplasia ossificans progressiva

Discovery offers hope to those trapped in 'second skeleton'
SHERYL UBELACKER
Canadian Press

U.S. researchers have isolated the defective gene responsible for one of the rarest and most "catastrophic" inherited diseases affecting humans — a condition that causes muscles and other connective tissues to turn into bone, imprisoning children for life in a second skeleton.

The disorder, known as fibrodysplasia ossificans progressiva (FOP), begins in childhood to progressively transform muscles, ligaments and tendons into ribbons, sheaths and plates of bone that cover and lock the joints, making movement impossible.

Researchers at the University of Pennsylvania and international colleagues have spent 15 years in a painstaking hunt for the gene, which they discovered in a region of chromosome 2. Their findings were reported Sunday in an online edition of Nature Genetics. "FOP is the most catastrophic disorder of extraskeletal ossification known to mankind," Dr. Fred Kaplan, director of the university's Center for Research in FOP and Related Disorders and a co-discoverer of the gene, told a Philadelphia news conference.

"The bone in FOP is perfectly normal in every way except it just should not be there." Dr. Kaplan, an orthopedic surgeon, said he was first exposed to FOP when he met two adults with the condition 18 years ago. Two years later, he met a child whose body was beginning to be locked in a carapace of extra bone — and that "lit the emotional flame" that set him and his team on a quest to find the cause and a cure for the devastating disorder.

The genetic abnormality occurs in only one in two million children, with an estimated 2,500 cases worldwide. The researchers have identified about 600 children and adults with the condition, including a handful in Canada. Children who inherit the defective gene seem normal at birth except for a tell-tale malformation of the big toe, which looks like a bunion. But between about age two and five, painful swellings that look like tumours "seize the skeletal muscles, tendons and ligaments and relentlessly transform them into bone," Dr. Kaplan said.

"Any attempt to remove this second skeleton leads to explosive growth of new bone formation and it is impossible to remove without causing more bone," Dr. Kaplan explained. "Even minor bumps and bruises cause catastrophic disability." Medical procedures that most of us take for granted — from immunizations to blood tests — can set off insidious bone growth. Needles for dental work can end up leaving an FOP patient with a permanently fused jaw.

FOP is often misdiagnosed as cancer, said Dr. Kaplan, citing the case of one young woman who had her arm amputated because doctors thought she had cancer. Not only did she lose her arm unnecessarily, but the surgery promoted even more connective tissue to harden into bone.

Eileen Shore, a professor of orthopedics and genetics at the university and co-principal investigator of the research, said FOP is caused by a single mutation in a gene known as ACVR1, which interferes with the protein switch responsible for bone-growth, turning it on when it should be shut off.

"This will lead to a direct and effective strategy for the treatment of this disease," said Dr. Shore, noting that scientists hope to find a drug that will block or get around the genetic trigger that spurs renegade bone growth in FOP. But their discovery could also lead to treatments for other conditions, such as unwanted bone that sometimes occurs after hip-replacement surgery, skull injury and osteoarthritis.

Learning to harness the switch could lead to methods of building bone in people with osteoporosis, the researchers added.

Amanda Cali, chair of the International FOP Association, said finding the gene has given hope to people with the disease and to their families. Eight Canadians, aged 10 to 40, are known to have the disorder, she said.

"This magnificent discovery allows the researchers to narrow the search for a treatment and a cure," Ms. Cali said from her home in Mountain Lakes, N.J.

Jeannie Peeper, 47, of Winter Springs, Fla., said from Philadelphia that her bony prison has left her completely immobilized, wheelchair-bound and totally dependent on others for care. She is able to move just her right hand and wrist.

"The gene discovery is an extraordinary gift to the FOP community and a monumental milestone on our road to a cure," said Ms. Peeper, who continues as a leader of the International FOP Association, despite the disabling condition.

"For me this day is truly the most extraordinary gift I have ever received, for the FOP gene to have been found in my lifetime."

Likening the ACVR1 mutation to a "molecular terrorist that turns a light bulb into an atom bomb," Dr. Kaplan conceded it will likely take years, even decades, before a treatment is found to reverse that process and liberate FOP patients from their extra armament of bone.

"There is a human component to this that is truly the inspiration for all that we do," said Dr. Kaplan, his voice breaking with emotion. "This is for us nothing less than a campaign for physical independence and personal freedom for these children.

"It was originally and it is today for and about the kids."

(Thanks to Dave Doldersum for this)

Taste The Future Of War

Scientists aim for 'sight' through tongue

Apr. 24, 2006. 04:19 PM

MELISSA NELSON

ASSOCIATED PRESS

PENSACOLA, Fla. — In their quest to create the super warrior of the future, some military researchers aren't focusing on organs like muscles or hearts. They're looking at tongues.

By routing signals from helmet-mounted cameras, sonar and other equipment through the tongue to the brain, they hope to give elite soldiers superhuman senses similar to owls, snakes and fish.

Researchers at the Florida Institute for Human and Machine Cognition envision their work giving Army Rangers 360-degree unobstructed vision at night and allowing U.S. navy SEALs to sense sonar in their heads while maintaining normal vision underwater — turning science fiction into reality.

The device, known as Brain Port, was pioneered more than 30 years ago by Dr. Paul Bach-y-Rita, a University of Wisconsin neuroscientist. Bach-y-Rita began routing images from a camera through electrodes taped to people's backs and later discovered the tongue was a superior transmitter.

A narrow strip of red plastic connects the Brain Port to the tongue where 144 microelectrodes transmit information through nerve fibres to the brain. Instead of holding and looking at compasses and bulky hand-held sonar devices, the divers can processes the information through their tongues, said Dr. Anil Raj, the project's lead scientist.

In testing, blind people found doorways, noticed people walking in front of them and caught balls. A version of the device, expected to be commercially marketed soon, has restored balance to those whose vestibular systems in the inner ear were destroyed by antibiotics.

Michael Zinszer, a veteran navy diver and director of Florida State University's Underwater Crime Scene Investigation School, took part in testing using the tongue to transmit an electronic compass and an electronic depth sensor while in a swimming pool.

He likened the feeling on his tongue to Pop Rocks candies.

"You are feeling the outline of this image," he said. "I was in the pool, they were directing me to a very small object and I was able to locate everything very easily."

Underwater crime scene investigators might use the device to identify search patterns, signal each other and "see through our tongues, as odd as that sounds," Zinszer said.

Raj said the objective for the military is to keep navy divers' hands and eyes free. "It will free up their eyes to do what those guys really want to, which is to look for those mines and see shapes that are coming out of the murk."

Sonar is the next step. A lot depends on technological developments to make sonar smaller — hand-held sonar is now about the size of a lunch box.

"If they could get it small enough, it could be mounted on a helmet, then they could pan around on their heads and they could feel the sonar on their tongues with good registration to what they are seeing visually," Raj said.

The research at the Florida institute, the first to research military uses of sensory augmentation, is funded by the U.S. Defence Department. The exact amount of the expenditure is unavailable.

Raj and his research assistants spend hours at the University of West Florida's athletic complex testing the equipment at an indoor pool. Raj does the diving himself.

They plan to officially demonstrate the system to navy and U.S. Marine Corps divers in May. If the military screeners like what they see, it could be put on a "rapid response" to quickly get in the hands of military users within the next three to six months.

Work on the infrared-tongue vision for Army Rangers isn't as far along. But Raj said the potential usefulness of the night vision technology is tremendous. It would allow soldiers to work in the dark without cumbersome night-vision goggles and to "see out the back of their heads," he said.

Anthropodermic Bibliopegy

Ancient Book May Be Covered In Human Skin

Ancient Book May Be Covered in Human Skin
Ancient Ledger That May Be Covered in Human Skin Found in England

LONDON Apr 8, 2006 (AP)— A 300-year-old book that appears to be bound in human skin has been found in northern England, police said Saturday.

The macabre discovery was made on a central street in Leeds, and officers said the ledger may have been dumped following a burglary.

Detectives were trying to trace its rightful owner and believe it may have been taken from a dwelling in the area.

Much of the text is in French, and it was not uncommon around the time of the French Revolution for books to be covered in human skin.

The practice, known as anthropodermic bibliopegy, was sometimes used in the 18th and 19th centuries when accounts of murder trials were bound in the killer's skin.

Anatomy books also were sometimes bound in the skin of a dissected cadaver. In World War II, Nazis were accused of using the skin from Holocaust victims to bind books.

In a brief statement, West Yorkshire police said the ledger, which contained handwriting in black ink, appears to date back to the 1700s, and they appealed to anyone who may be able to help identify the owners of the item to contact authorities.

West Yorkshire Police put two photographs of the book on their Web site, but officers were unable on Saturday to answer any questions about it, including the book's subject matter.

On the Net:

http://www.westyorkshire.police.uk/section-item.asp?sid12&iid2240

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