Brothers in Search of a Cure

He’s told the story dozens of times. About how he started showing symptoms when he was 28 toward the end of medical school. About the unusual weakness he felt in his fingers that made it difficult to play his guitar. About how it became harder and harder to go up a flight of stairs. It’s the story he’s told numerous times about the rare genetic disease he shares with his brother that has confined them to a wheelchair and will continue to waste away at their muscles, unless they find a cure.

Babak Darvish, MD, 35, sat comfortably in his powered wheelchair at the VA Hospital on Wilshire Boulevard. He is a staff physician and the Director of the Inpatient and Geriatric Rehabilitation Consult Service.

He described his disease, Hereditary Inclusion Body Myopathy or HIBM, with much ease, as his mini entourage consisting of a few family friends and staff strolled in and out of his office to hand him a document or bring in his dinner, almost in a celebrity-like fashion.

HIBM is a rare condition that affects middle-eastern Jews, like Babak, an Iranian Jew, causing progressive muscle wasting and weakness. Symptoms usually begin between the ages of 20-40 and may entail 10-15 years to fully develop, typically leading to total disability. Two copies of the mutated gene are needed to develop HIBM since it is recessively inherited. Thus, when both parents are carriers, each of their offspring has a 25 percent chance of developing it.

Danny is Babak’s older brother. Though 2 years apart, they developed symptoms around the same time. The brothers were symptom-free throughout their teenage lives; fit, athletic and active. Apprehension loomed when their limbs grew weak in their late 20s. "No medical professional could give us a satisfactory answer." Explains Babak. "At that point, it was clear to me what needed to be done." As medical students initially drawn toward subspecialty fields of surgery, their new mission was to be the last ones affected by the debilitating disease.

The disease was uncommon and unidentified at the time, which stimulated their initiative to fully embrace the concept of finding a cure. Danny has since stopped practicing medicine altogether and dedicates his time solely to HIBM research.

Advancement of Research for Myopathies, (ARM), was founded in 1997 to fund HIBM research. They raise public awareness, award grants to scientists who are willing to help with biomedical research, and who in 2001, located the gene mutation responsible for HIBM.

ARM was gathered in Babak's office that night for their weekly meeting. Everyone was exceptionally attentive, available to tend to his every need, "Hey Bobby, you need anything?" There was an occasional knock at his office door from a member checking up or having a “quick question.”

Babak seems healthy and well, but when he makes certain movements, his difficulties are apparent. He has trouble reaching for objects or raising his arm, but can hold a pen, write, and shake hands when introducing himself. "I stopped driving 2 years ago as it became progressively more difficult to keep control of the vehicle. I felt I was no longer safe on the road."

HIBM was often misdiagnosed for Multiple Sclerosis or Muscular Dystrophy. They might have similar symptoms but they function very differently.

Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System, which includes the brain and spinal cord. Predominantly, it is a disease of the "white matter" tissue. The white matter is made up of nerve fibers, which are responsible for transmitting communication signals both internally within the CNS and between the CNS and the nerves supplying the rest of the body.

In general, people with MS can experience partial or complete loss of any function that is controlled by, or passes through, the brain or spinal cord.

Muscular Dystrophy, (MD) is a disease in which the muscles of the body get weaker and weaker and slowly stop working. It affects muscles throughout the body including the heart, where HIBM does not affect the heart at all.

The dystrophin gene is carried on the X-chromosome, therefore young men are more susceptible to dystrophin damage because they have only one X-chromosome.

MD affects all muscles because Dystrophin is found on all types of muscle tissue including 'cardiac' (of the heart) and 'smooth' (of the digestive tract). Unlike skeletal muscle, these muscles are involuntary, meaning that they cannot be moved at will. HIBM, on the other hand, only affects skeletal muscles. It is the most common genetic disorder in people of Iranian-Jewish descent. Yet, most primary care physicians have never heard about it. Because it only affects a few hundred patients worldwide, it is considered a rare “orphan” disease.

Many people with the disease or those who have loved ones with HIBM do not endorse Danny and Bobby's efforts to go public. After all, it is a social stigma to have a genetic disease in the Persian Jewish community. One patient lies about why he limps to ensure that his daughters will marry while another was shamed and compelled to move to another state to avoid disgracing his family.

There are those affected, however, who keep their heads held high, at least to the best of their ability.

I’m not ashamed. Why would I be ashamed?’ Helen Shirazi, 47, is in the advanced stages of the disease, unable to move any part of her body except her fingers, mouth and eyes. Her grandfather was Iranian, but she was born in Israel. Helen was referred to the Darvish’s only several months ago and was recently diagnosed with HIBM. Doctors could not make a proper diagnosis tracing back to the time she started dragging her feet at 20 years old. “One doctor told me I had one year to live.” She started to choke up, but held back her tears. “He destroyed my spirit, my soul.”

She met and married Shalom after her first marriage collapsed. Shalom is a cheerful man with a loud sense of humor who moves about doing little things for his wife, making her laugh and keeping her inspired.

Before we were married, he offered to wash me, to bathe me. He read my thoughts, he felt me.” She completely lost her ability to walk by the time they wed, so his role in the marriage quickly took shape; cooking, cleaning and doing all the household chores as well as helping his disabled wife cope, even when he suffered from severe back pain. They hired a helper just two years ago when Shalom needed surgery.

There’s nothing wrong with her, she’s healthy and normal.” Shalom believes his own words despite the unfortunate truth that his wife’s limp body can only lie there, bed-ridden, motionless, helpless, with a limited view of what’s directly in front of her. Helen confesses to her moments of grief, but is motivated and mentally active for the most part.

I’m not disabled, and I’m not in denial either. I can move the world.” She has undeniably moved her own world, majoring in Psychology at Cal State Northridge, faced with the challenge of getting to class, relying on her helper to take notes and dictating her assignments to any student willing to take the time.

Her wish is to write an inspirational biography about how everything could be taken away except the spirit and the mind. “Don’t underestimate me.”

Helen is one of the few patients eager to share her tale or “come out.” There are patients in Iran, Israel, across Europe, and on the East and West Coasts, but only about 500 known cases worldwide, which is why the availability of public funding for research is extremely limited. HIBM is too rare for pharmaceutical companies to deem it as a lucrative investment.

Fortunately, ARM funding helps operate and maintain the HIBM Research Group in Encino, the lab, where in addition to facilitating the genetic engineering and the ultimate production of the animal model for HIBM in mice, serves as a central suppository of research samples, tissues, reagents, and late-breaking developments of antibodies, for use by all investigators involved in HIBM Research. This levels the playing field and stimulates collaboration among the different researchers, who are sponsored by ARM to move research forward.

Although there is no treatment so far, the Darvish’s are hopeful that in the next decade there will be a treatment to prevent or inhibit the process of HIBM.

I am optimistic that this won’t exist in the next generation. There are teen-agers who have no idea what’s in store for them. If I could prevent a young girl or boy from ending up in a wheelchair like me, I’ve done my job.” Babak predicts HIBM will be treatable in 5-10 years.

Two extraordinary women who have contributed to making Danny and Bobby’s jobs and lives much less troublesome are Sandra and Sheila, their wives. Babak’s first marriage failed because his wife at the time could not deal with the progression of his illness.

But Sandra has been passionate and sympathetic since they met in Canada in 2002. At the time Bobby was already in a wheelchair, attending a medical conference in Vancouver to promote HIBM research, while Sandra had taken a part-time job as a tour guide.

She showed me around the city and I knew I never wanted to be away from her.”

Sandra is devoted and kind, showering her husband with unconditional love. But as Bobby so clearly puts it, “if it isn't unconditional, it isn't love!” Sandra helps Bobby dress, use the restroom and is usually only an earshot away. HIBM has not tainted their desires to carry on a normal life either.

We want kids and we’re half way there.” Apparently, HIBM has no influence on intimacy. “You just have to be a creative lover.” Though confined to a wheelchair, HIBM sufferers are not paralyzed. It is not a disease that affects the nerves, therefore sensation is maintained throughout the body.

Babak is the more social and optimistic of the siblings. Danny is upbeat, but more often reminisces of active times when he could ski, or walk to the mailbox, or even get out of bed. He misses the abilities he once had that the rest of the world takes for granted.

Most people in a wheelchair have a static condition. They know it won’t get any worse. But HIBM is progressive.” Babak explains.

The minute you get used to one dysfunction, another one kicks in.” Danny finishes his brother’s thought.

Danny and Sheila have a sacred marriage, as Sheila is also an incredibly tender, warm and energetic woman from the Philippines. It seems that Sheila and Sandra have found a support system in one another; they have much in common caring for physically dependent men.

My arm is getting stronger because I have to turn him over several times in the middle of the night.” Sheila jokes as Sandra giggles in agreement.

Me too!”

Sandra and Sheila have embarked on their husbands’ goals and work hard on a daily basis whether it is in the lab, going to meetings or just being emotionally available for their spouses.

Another female backbone in Danny and Bobby’s lives is their mother, Shuku. Not only is she ARM’s co-founder and spokesperson, but she also engages in day-to-day planning and fund raising.

In the meantime, Bobby and Danny are still physically able to walk with a great deal of help though they take comfort in their wheelchairs.

I walk around more than you do Bob!” His younger brother shrugs it off. “Okay, okay, I’m lazy.” But witnessing Danny walk is painful. He struggles with every movement like a one-year-old taking his first steps, unbalanced and unsure of whether he will tip over before reaching his destination.

The remarkable thing about the Darvish brothers is that they are working toward finding a cure for their own disease. Their initial drive created ARM, which supplies the funds needed to carry out research. Their continued persistence helped find the gene responsible for HIBM. Without their involvement, the gene would most likely still be lost. Their sustained ambition will further medical advancements. The disease would have remained stagnant without them.

Donations, funds and contributions are vital in speeding up HIBM research and developing an effective treatment. Community awareness and support is key to moving the research forward.

Finding a cure for Hereditary Inclusion Body Myopathy can ultimately result in healing related diseases in the world, but financial help is critical.

Bobby’s advice for all patients with a severe medical condition: “All I can say to anyone with any kind of a disability is ‘make exceptional use of what you have.’” Danny agrees: “Life doesn’t have to be so bitter or any worse.”

But the reality lingers: time is running out.

Please help Daniel and Babak as well as hundreds of others fight HIBM by donating to: Advancement of Research for Myopathies, PO Box 261926, Encino, CA 91436

For more information on HIBM, go to: www.hibm.org