It’s been a little over a decade since two strapping brothers in the prime of their lives noticed their bodies were starting to give out on them.
They were medical students in their late 20s, studying to be surgeons.
Skiing, basketball and bodybuilding were some of their free-time activities.
Babak Darvish, the younger brother, noticed his fingers were going numb, and it was hard to play his guitar.
Daniel Darvish, two years older, began to notice similar symptoms at about the same time.
After years of exhaustive research and consulting renowned physicians and scientists in the fields of muscle disorders and genetic diseases, the brothers diagnosed themselves: They had hereditary inclusion body myopathy (HIBM), a genetic disorder found primarily in Iranian Jews.
The rare genetic disease eventually leads to total paralysis.
Today, the brothers, both medical doctors, lead a team of scientists and researchers working to develop a treatment for HIBM. They established a research lab in Encino in early 2000, before moving it to Reseda two years ago.
“Working with several research teams worldwide, [we] believe they may already have more than one effective treatment, yet it could take many years before realizing success, because patients will have to be followed over years in clinical trials to determine if and how well each treatment works,” Daniel Darvish said.
"An effective treatment is expected to halt the disease progression and stabilize the patient's muscle strength," he said. "Thus, when started very early or before disease symptoms begin, we hope it will prevent muscle loss altogether.
"Time is of the essence for many patients,” he said.
Babak and Daniel were born in Iran and immigrated to America during their middle school years.
Their mother is a genetic carrier of the disease.
The Darvish brothers, now 41 and 43, respectively, have lost the use of their arms and legs. They use wheelchairs and are dependent on others for their physical needs.
A race against time
In the early 2000s, HIBM was often misdiagnosed as multiple sclerosis or muscular dystrophy. HIBM symptoms of muscle weakness typically begin between the ages of 20 and 34 and can take another 10 to 15 years to become severely debilitating.
In 1997, there was no definitive diagnosis for HIBM, no public information about it, no ongoing research, no treatment and no hope for those affected.
In 2002, Daniel decided to quit his private medical practice and devote almost all of his time to HIBM Research Group, an accredited, nonprofit molecular laboratory dedicated to advancing research of the disease.
"When I realized that I was going to be disabled—slowly, relentlessly and without reason or justice—I gained courage," Daniel wrote on his research website. "When I met others with the same problem, I learned compassion. When we realized that it could be healed scientifically, we touched hope."
He had started in 1999 by developing Advancement of Research for Myopathies, a fundraising component of the brothers' battle against HIBM, to finance research and development. Babak Darvish is the chairman of its board.
They began with a shoestring budget of $10,000, and this year, private donations and grants upped the annual ante to $353,000.
Their mother, Shuku Darvish, and Daniel's wife, Sheila, along with board members and many volunteers, have set a goal of raising $500,000 next year. An estimated 84 percent of the money they raise is spent on research.
Daniel has a team of 13 part-time and volunteer scientists and researchers who work on developing a cure.
The goal is to eradicate the disease if detected early, or slow down its progress, if onset is already apparent.
Living with the disease
Despite losing the use of their arms and legs, the Darvish brothers carry on.
It can take them up to three hours from the time they wake until the time they begin to seize the day from their Sherman Oaks homes. The brothers live in adjacent condominiums.
Both are married and have one young son each.
No adults have slept through the night for years, because the brothers need to be turned over in bed a couple of times a night to alleviate their pain. They can’t groom or feed themselves, or get in and out of bed, so they depend on help. Usually it is their wives who perform these tasks, but they sometimes also use paid help.
“I’m like a glove that fits well with Daniel,” said Sheila, his wife of eight years.
Babak and Daniel still have some muscle twitching and minor movement, but their fingers are weak and they manage with increasing difficulty.
“Without treatment soon," said Daniel, they will be completely paralyzed. “We still have sensation, which is good. This disease affects you horribly. Some days are better than others.”
Daniel rises at 7 a.m., and usually arrives at the Reseda lab at about 9 a.m. At 4 p.m., he leaves for physical therapy, which includes stretching and meditation exercises. Then he heads home.
Once there, he does more research, reads or types for about four hours and doesn’t lay his head down to sleep until the wee hours. Then, the sun rises and his day starts again.
Meanwhile, Babak treks to the Veterans Hospital in West Los Angeles, where he works full time as a physical medicine and rehabilitation physician.
He has a paid assistant and uses gadgets such as speech-recognition software to
help him do his job at the hospital.
High hopes for a cure
Although HIBM causes severe disability in the prime of life and leads to quadriplegia, the Darvish brothers believe a cure is within reach.
“[A cure] will slow/halt the disease. So time is of the essence,” said Daniel, whose speech sounds unaffected by the disease. “We would love to preserve what we are able to do now—hold our chin up, look people in the eye, speak. Many advance patients need neck and trunk braces just to be able to sit up.”
Through their efforts, the disease can now be diagnosed with a mouth swab. Testing is available for anyone. Research has led to finding the responsible gene mutation.
At the lab, cell cultures have been established. A distribution center provides research samples, much-needed biomaterials and reagents to support worldwide research.
Dr. Yadira Valles-Ayoub of the Darvish lab has worked at finding a treatment for seven years.
Valles-Ayoub said the affected gene was discovered by an Israeli team that worked with the Darvish lab to identify it through blood samples sent to them by patients' families from all over the world.
“Identifying patients with different mutations added to the evidence that HIBM is indeed caused by mutations on the GNE gene and allowed us to identify many non-Iranian patients,” Valles-Ayoub said. “The number of available patients for clinical trial is very important. The higher the number of available patients, the faster we might be able to develop a treatment.”
Valles-Ayoub said it is very important that a child be identified early as having the disease.
“If we can do the gene correction before he is limping, the chance he will be perfect is greater,” she said.
Valles-Ayoub said that although her boss, Daniel, doesn’t have full use of his arms and legs, he has a “big brain and he is honest.” She believes in the team's work, she said.
Because HIBM is such a rare disease, little financial help comes from government and large institutions.
Darvish said, however, the landscape is slowly changing and that federal granting agencies, private donors and pharmaceutical companies are becoming increasingly interested in rare diseases.
“This is partly due to escalating difficulties in developing treatments for common disorders and advantages offered by the Orphan Drug Act,” Darvish said.
The Orphan Drug Act encourages pharmaceutical companies to develop drugs for diseases with small markets, unlike those diseases that affect large populations, such as AIDS.
In 2010, the U.S. Food and Drug Administration boosted research efforts for the disease when it gave “orphan drug” status to the HIBM Research Group. The group also has received support from the Muscular Dystrophy Association.
For more information about hereditary inclusion body myopathy, go to HIBM.org.