Israeli Scientist Adapts Antibiotic That May Fight Genetic Disease

Something New: Timor Baasov has modified a highly toxic antibiotic so that it might be used to repair genetic mutations.
COURTESY OF THE AMERICAN TECHNION SOCIETY
Something New: Timor Baasov has modified a highly toxic antibiotic so that it might be used to repair genetic mutations.

By Talia Bloch

Published August 19, 2009, issue of August 28, 2009.
  • Print
  • Share Share

A team of researchers in Israel has made a breakthrough in modifying an until-now highly toxic antibiotic so that it might one day be used to repair defective genes that cause diseases such as cystic fibrosis, Usher syndrome, Duchenne muscular dystrophy and even some cancers.

Timor Baasov, a professor of chemistry at the Technion-Israel Institute of Technology, has been able to modify the antibiotic gentamicin so as to make it both effective in treating a certain type of genetic mutation and nontoxic enough so that it might be tolerated by humans when ingested on a regular basis.

“Gentamicin is very toxic, and it itself cannot be used for treatment,” Baasov said. “We chemically modified it and generated a new compound with a much lower toxicity.”

The new compound is called NB54, and Baasov has been able to demonstrate its effectiveness in treating test tube cell cultures taken from patients with cystic fibrosis.

Baasov and his team published their findings online in March in the Journal of Medicinal Chemistry. Since then, a team of researchers at the University of Alabama, led by David Bedwell, has had promising results using NB54 in a live mouse.

“We have very good data, very promising data from the in vivo experiment,” Baasov said, commenting on his collaboration with Bedwell.

NB54 works by allowing cells to read through a type of mutation called a premature stop mutation, a random piece of scrambled genetic code that stops the cell in the middle of making a healthy protein. “It’s like a train going down a track and then suddenly stopping dead before it gets to the end of the track,” Bedwell said of the mutation’s effects. NB54 allows the cell to continue and complete the necessary protein.

Bedwell, a professor of microbiology and genetics and an expert in stop mutations, said that this type of mutation is responsible for between 10% and 15% of all genetic diseases and usually results in the most severe forms of a particular genetic disease.

Whereas most cases of cystic fibrosis — which is the most common genetic disorder among Caucasians and can be caused by a number of different mutations — are not caused by stop mutations, approximately 70% of cystic fibrosis cases among Ashkenazic Jews are caused by such a mutation.

A second lab at the Technion in Haifa has tested NB54 on another disease arising among Ashkenazic Jews, Usher syndrome, which causes deafness and progressive blindness. Tamar Ben-Yosef, a senior lecturer in the faculty of medicine at the Technion who in 2003 discovered the mutation responsible for Usher syndrome type I — the most severe form of the disease — in Ashkenazic Jews, has tested NB54 and found it was able to suppress the mutation in cell cultures.

“I want to stress that we are very, very far from testing it on human beings,” cautioned Ben-Yosef, who recalled that her frustration over finding the mutation but having no cure for the disease led her to partner with Baasov’s lab. Nevertheless, she called NB54 a breakthrough, because it’s the first time a chemist “used his knowledge of chemistry to modify this compound in a rational way for the desired effect.”

“NB54 is not a final solution,” Bedwell remarked. “We need to keep going to improve it.”

Scientists proved some years ago that gentamicin allows cells to read through stop mutations, but its toxicity remained an issue. Gentamicin is one of a class of highly toxic antibiotics called aminoglycosides that doctors only use as last-resort drugs when all other antibiotics have failed to be effective. Taken in the doses necessary to kill bacteria, gentamicin is tolerable by humans. But taken on a regular basis over a lifetime, as would be required to treat a chronic genetic disorder, gentamicin could lead to hearing loss, kidney failure and even death.

Baasov, who has been working with aminoglycosides for some five years now, has found that by stripping gentamicin of its antibacterial properties it remains effective in suppressing stop mutations, but becomes much less toxic for humans. Since announcing his findings in March, said Baasov, he has had inquiries from labs around the world eager to test out his compound.


The Jewish Daily Forward welcomes reader comments in order to promote thoughtful discussion on issues of importance to the Jewish community. In the interest of maintaining a civil forum, The Jewish Daily Forwardrequires that all commenters be appropriately respectful toward our writers, other commenters and the subjects of the articles. Vigorous debate and reasoned critique are welcome; name-calling and personal invective are not. While we generally do not seek to edit or actively moderate comments, our spam filter prevents most links and certain key words from being posted and The Jewish Daily Forward reserves the right to remove comments for any reason.





Find us on Facebook!
  • Israeli soldiers want you to buy them socks. And snacks. And backpacks. And underwear. And pizza. So claim dozens of fundraising campaigns launched by American Jewish and Israeli charities since the start of the current wave of crisis and conflict in Israel and Gaza.
  • The sign reads: “Dogs are allowed in this establishment but Zionists are not under any circumstances.”
  • Is Twitter Israel's new worst enemy?
  • More than 50 former Israeli soldiers have refused to serve in the current ground operation in #Gaza.
  • "My wife and I are both half-Jewish. Both of us very much felt and feel American first and Jewish second. We are currently debating whether we should send our daughter to a Jewish pre-K and kindergarten program or to a public one. Pros? Give her a Jewish community and identity that she could build on throughout her life. Cons? Costs a lot of money; She will enter school with the idea that being Jewish makes her different somehow instead of something that you do after or in addition to regular school. Maybe a Shabbat sing-along would be enough?"
  • Undeterred by the conflict, 24 Jews participated in the first ever Jewish National Fund— JDate singles trip to Israel. Translation: Jews age 30 to 45 travelled to Israel to get it on in the sun, with a side of hummus.
  • "It pains and shocks me to say this, but here goes: My father was right all along. He always told me, as I spouted liberal talking points at the Shabbos table and challenged his hawkish views on Israel and the Palestinians to his unending chagrin, that I would one day change my tune." Have you had a similar experience?
  • "'What’s this, mommy?' she asked, while pulling at the purple sleeve to unwrap this mysterious little gift mom keeps hidden in the inside pocket of her bag. Oh boy, how do I answer?"
  • "I fear that we are witnessing the end of politics in the Israeli-Palestinian conflict. I see no possibility for resolution right now. I look into the future and see only a void." What do you think?
  • Not a gazillionaire? Take the "poor door."
  • "We will do what we must to protect our people. We have that right. We are not less deserving of life and quiet than anyone else. No more apologies."
  • "Woody Allen should have quit while he was ahead." Ezra Glinter's review of "Magic in the Moonlight": http://jd.fo/f4Q1Q
  • Jon Stewart responds to his critics: “Look, obviously there are many strong opinions on this. But just merely mentioning Israel or questioning in any way the effectiveness or humanity of Israel’s policies is not the same thing as being pro-Hamas.”
  • "My bat mitzvah party took place in our living room. There were only a few Jewish kids there, and only one from my Sunday school class. She sat in the corner, wearing the right clothes, asking her mom when they could go." The latest in our Promised Lands series — what state should we visit next?
  • Former Israeli National Security Advisor Yaakov Amidror: “A cease-fire will mean that anytime Hamas wants to fight it can. Occupation of Gaza will bring longer-term quiet, but the price will be very high.” What do you think?
  • from-cache

Would you like to receive updates about new stories?




















We will not share your e-mail address or other personal information.

Already subscribed? Manage your subscription.