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CAMBRIDGE, Mass. — When Sharif Tabebordbar was born in 1986, his father, Jafar, was 32 years old and was already showing signs of wasting disease. The mysterious illness would determine Sharif’s life.

When Jafar Tabebordbar was in his 30s, he could walk, but stumbled and often lost his balance. Then he lost the ability to drive. At the age of 50, he could use his hands. Now he has to support the other with one hand.

No one could answer the question that plagued the Sheriff and his younger brother Shayan: What was this disease? And would they develop it the way their father did?

As he grew up and watched his father slowly decline, Sharif vowed to solve the mystery and find a cure. His pursuits led him to a PhD in developmental and regenerative biology, the most competitive echelons of academic medical research, and an exploration. Published in Cell magazine in SeptemberThis could transform gene therapy – the drug that corrects genetic defects – for nearly any muscle wasting disease. This includes muscular dystrophies, which affect about 100,000 people in the United States, according to the Muscular Dystrophy Association.

Scientists often use an inactivated virus called adeno-associated virus, or AAV, to deliver gene therapy to cells. However, Dr. Damaged muscle cells such as those affecting Tabebordbar’s father are difficult to treat. Forty percent of the body is made of muscle. In order to infect these muscle cells, researchers need to administer very large doses of the drug. Most viruses reach the liver, damaging the liver and sometimes killing patients. Trials stopped, researchers blocked.

Dr. Tabebordbar was able to develop viruses that went directly to the muscles—very few made it to the liver. Its discovery may allow treatment with a fraction of the dosage and without disabling side effects.

Working on therapies for muscle diseases at the University of Washington and Dr. Not involved in Tabebordbar’s research, Dr. Jeffrey Chamberlain said the new method “could take it to the next level.” Accurately targeting almost any tissue that is just beginning to be considered as gene therapy targets, including brain cells.

And director of the National Institutes of Health, which helped fund the research, Dr. Francis Collins said in a statement: blog post He said it has “the potential to target other organs”, thus “probably providing treatments for a wide variety of genetic conditions.”

Dr. Tabebordbar’s small office at the Broad Institute has a glass door that leads directly to the lab bench. It’s not like home. No photographs, books, or papers were scattered on the white counter that served as a table. Even the whiteboard is clean. There, he’s fed up with caffeine, usually working 14 hours a day, except on days when he plays football with a band at MIT.

Dr. “Incredibly productive and incredibly effective,” said Amy Wagers, Ph.D. of Tabebordbar. consultant and professor and co-chair of the stem cell and regenerative biology division at Harvard. “She works hard and has incredible passion and incredible dedication. And it’s contagious. It infects everyone around her. It’s a real talent – the ability to take a greater vision and communicate it.”

Dr. Tabebordbar and his wife live in Cambridge, Mass. She likes to cook Iranian food, and every Thanksgiving she throws a banquet in her small apartment for a dozen of her friends. He listens to Persian music, podcasts or audiobooks while working at the lab bench. He likes biographies and talks about a passage he finds meaningful in the autobiography of one of his heroes, the English football player Michael Owen.

Mr Owen writes that his reaction softened when he learned that he had been named European player of the year in Europe. “All I wanted to do was score the next goal, score a hat-trick and lift the next trophy,” Mr Owen wrote. “Looking back, I was ruthless about it and I have no doubt that this mindset was the key to my success.”

“It’s like me,” said Dr. tabebordbar. “It’s unbelievable that we’ve succeeded, but now”—she snaps her fingers—”we need to get started. What’s next?”

Dr. Tabebordbar was born in Shiraz, Iran, but moved to Rasht when he was 9 years old.

Based on his score in a national exam, he was accepted into a high school that is part of Iran’s National Organization for the Development of Extraordinary Talents. There, he focused on the biological sciences, motivated by his drive to help his father. Her mother, Tahereh Fallah, who wanted to become a doctor but could not continue her education in Iran, forced Sharif and her brother to be successful and celebrated their success.

After high school, Sharif was determined to be one of eight to 10 students in the country admitted to an accelerated program at Tehran University. He attains a bachelor’s, master’s and doctorate degree in just nine years.

“This was my dream,” he said. “I had to study really hard for this exam – English, Arabic, science.” Paid – seventh out of 1.3 million.

He specialized in biotechnology at Tehran University. Four and a half years later, he got his master’s degree, but started applying for a PhD. Programs at top international universities are researching muscular dystrophies in the hopes that it will lead to a discovery that might help his father. Harvard’s Dr. He went to Wagers’ lab.

From the very beginning, the question preoccupied him: What caused his father’s illness?

When his father arrived at Harvard to attend his 2016 graduation ceremony, Dr. Tabebordbar seizes the moment to sequence Jafar’s genes and solve the mystery. No mutation found.

“How is this possible?” Doctor Tabebordbar asked.

More detailed and sophisticated testing eventually revealed the answer: His father has an exceptionally rare genetic disorder, facioscapulohumeral muscular dystrophy, or FSHD, that affects an estimated four to 10 out of every 100,000 people. It is not caused by a mutation in a gene. Instead, it is caused by a mutation in a space between genes that results in the secretion of a toxic chemical that kills muscle cells.

Dr. Tabebordbar was horrified to learn that he had a 50-50 chance of inheriting the mutation from his father. If he had, he would have contracted the disease.

Tested by a friend who called him with the result.

Dr. Tabebordbar had inherited the mutation, but – surprisingly – the mutated gene was missing the last piece of toxic DNA, which prevented the condition from occurring.

“You are the luckiest of the unlucky,” his friend remembered saying.

Dr. In Wagers’ lab, Dr. Tabebordbar studied muscular dystrophy using the gene editing technique CRISPR. He tried to use AAV to transport CRISPR enzymes to muscle cells where he could correct the mutation. As others have found before him, it was not that simple.

In 2004, from the University of Washington, Dr. Chamberlain reported that AAV could deliver gene therapy to the muscles of mice. However, Dr. Chamberlain recalled that treating it required “astronomical doses” of the disabled virus.

Dr. “At these very high doses, you’re on the verge of other problems,” Chamberlain said, and the liver was overwhelmed.

Despite the risk of high doses of AAV, clinical trials of gene therapy are ongoing for patients with muscle diseases, but only in children. It can handle smaller bodies with lower doses containing less virus.

Gene therapy with AAV has been approved for spinal muscular atrophy, a fatal muscle disease.

Gene therapy researcher at Stanford, Dr. “This is a terrible disease,” said Mark Kay. Even at child-sized doses, some children died from the drugs used to save them.

Dr. “But if you don’t treat them, they’ll die of disease,” Kay said.

Dr. Tabebordbar’s project at Harvard also suffered from overdose problems. although he managed to correct muscular dystrophy in mice – a success reported simultaneously by two other labs – this was no guarantee that gene therapy would work in humans. Different species, even different types of mice, may respond differently to the same gene therapy. And AAV doses were dangerously high.

Dr. A disease such as the one that Tabebordbar’s father suffered from is particularly difficult. More common muscular dystrophies are caused by a mutation that deprives patients of a particular protein. Gene therapy should replenish this protein in some but not in some muscle cells.

Dr. The disease that afflicts Tabebordbar’s father involves a toxic substance produced by about one percent of the muscle cells that then spreads to the muscle fibers. To get rid of this toxin from the muscles, gene therapy must reach every muscle cell.

Dr. “This is a much higher bar,” Tabebordbar said.

After graduating from Harvard, Dr. Tabebordbar thought he had a chance to develop a gene therapy for muscular dystrophy at a biotech company. But about a year later, the company called everyone into a conference room to say there would be a restructuring and that the muscular dystrophy program would be removed. Dr. Tabebordbar knew he had to go elsewhere.

He took a position in the Pardis Sabeti lab at the Broad Institute and got to work. His plan was to mutate millions of viruses and isolate those that went almost exclusively to the muscles.

The result was what he had hoped for – viruses residing in muscles, mice and monkeys, which makes it much more likely to work in humans.

As scientists know, most experiments fail without anything succeeding, and this work has only just begun.

Dr. “I’m going to do 100 experiments and 95 won’t work,” Tabebordbar said.

But he said that this is the personality expected of a scientist.

“The mentality I have is, ‘this isn’t going to work’. It makes you very patient.”

Dr. Chamberlain, Dr. With all the preclinical work that Tabebordbar has done, new viruses could move into clinical trials in as little as six months to a year, he said.

Now Dr. Tabebordbar took his next step. Apart from his brief stint in biotechnology, he spent his life in academia, but decided he wanted to develop drugs. About a year ago, she co-founded a pharmaceutical company called Kate Therapeutics, which would focus on gene therapy for muscle diseases and move there for the next phase of her career.

He hopes that his work will save others from suffering. Still, his father’s fate depends on him. Jafar Tabebordbar missed the window where it might still be possible to help him.

“He was born very early,” his son said.