Israeli Prof. Timor Baasov has found a way to modify antibiotics, making them powerful drugs against genetic diseases.Antibiotics are no doubt the wonder drug of the 20th century. Before them, people could die from simple bacterial infections. Now, new groundbreaking research from Israel shows that a common antibiotic has the power to repair genetic diseases like cystic fibrosis, cancer and muscular dystrophy.

The Israeli team headed by Prof. Timor Baasov of the Technion – Israel Institute of Technology, has modified a common antibiotic, one without toxic effects, and which is programmed to fix “nonsense” mutations in genetic diseases. Nonsense mutations are mutations in a sequence of DNA which causes it to prematurely stop reading the RNA, resulting in an incomplete and non-functional protein being created.

Doctors have long known that antibiotics could work as a possible treatment for repairing the nonsense mutation, something that occurs in about 10-15 percent of most genetic diseases. Using available antibiotics, science was not yet been able to find a solution that would work without toxic effects.

Since releasing the news of the new compound, called NB54, based on the common antibiotic gentamicin, Baasov has been flooded with queries from investigators all over the globe excited to test it, he tells ISRAEL21c. The findings were published online in March in the Journal of Medicinal Chemistry.

Powerful, non-toxic adaptation of common antibiotic

“Why is this a breakthrough?” he asks. “This is the best compound that can [work to repair genetic diseases],” he explains. This includes, “cystic fibrosis, and thousands of different genetic diseases. None of them has a real treatment,” says Baasov.

“The issue is that there have only been very old developments,” he says, citing research from 1985 that already showed how small molecules such as antibiotics can work to fix genes.

“Developments have been done over the last 20 years by medical doctors and people working with medicine have used only existing antibiotics and no one worked at improving antibiotic activity,” he explains.

“The ones that they had been using are not powerful enough for fixing genes, and are very toxic at concentrations needed to be used for the treatment.”

The Technion lab investigated the mechanism that would fix genes. The chemists, who also specialize in biochemistry, then redesigned existing antibiotics to have less toxic effects, and to be more versatile and powerful.

Gentamicin is from a group of antibiotics known as aminoglycosides, which are used to treat a wide range of bacterial infections. It is commonly used to treat enlarged prostate glands, chest infections, urinary tract infections and infected wounds or burns. Previous studies find gentamicin can work to counteract genetic diseases when mutations cause disruptions of the development processes of proteins.

Compound working in cystic fibrosis

The drug enables ribosomes, which carry out protein synthesis, to ignore these genetic disruptions and generate healthy, full-length functional proteins instead.

But until now, doctors were not able to prevent the toxic side effects needed for the treatment. Profound hearing loss was one of the unwanted shortcomings of using this antibiotic for treatment.

“We have shown our lead compounds are more powerful than existing antibiotics and much less toxic. We also have data on preclinical studies on cystic fibrosis that it works well. This is the very new direction that shows how chemistry can modify toxic compounds to be useful as a drug,” says Baasov.

“We’ve created a new purpose for aminoglycosides by removing their traditional, natural actions as antibiotics. The loss of their antibacterial activity makes them highly selective, less toxic, and allows for their use in repairing ‘wrong’ genes in human beings,” he adds.

Now having paved the way for drug developers, Baasov plans to license this new compound to investigators looking to solve some of the most troubling genetic diseases. With the compound already described, and patents pending, he expects it could be less than a few years for a new cystic fibrosis drug to be on the shelf, granted the right investment and clinical goals are met.

A medical missile aimed at hearing loss and cancer cells

As scientists, and not business people, the researchers also continue their quest to make their discovery better. “This is a missile. It’s a new compound,” Baasov tells ISRAEL21c. “It’s the best of the best in the world, and it might be a new drug,” he adds cautiously, as scientists tend to not make claims until the clinical evidence is in.

The only lab in Israel dealing with sugar chemistry, “We are a pretty unique lab, combining chemistry, biochemistry, and biological chemistry,” says Baasov.

In cystic fibrosis, a condition which affects about 1 in every 2,500 Caucasian children in the United States, and less in other racial groups, except in Ashkenazi Jews where it’s higher, Baasov’s compound could treat 10-15 percent of all sufferers, he anticipates.

“The cancer issue is one of the things I had no time to deal with yet, but there are lots of different possibilities. One is that there are many anti-cancer drugs that are already developing some drug resistance, and are not powerful anymore. One of the kinds of resistance is a special mutation that we can treat. Our compound can avoid resistance so the anti-cancer drugs are used in combination with existing drugs,” he notes, adding that targeting cancer is his next goal.

Baasov has also started a collaboration with Dr. Tamar Ben Yoseph from the Technion’s Faculty of Medicine to treat the genetic defects of hearing loss. She is a geneticist and expert on Usher Syndrome, a rare disorder that causes deafness and blindness, and approached Baasov about a joint effort to synthesize new and efficient, but non-toxic derivatives of antibiotics to treat genetic defects.

“We are making sense from ‘nonsense.’ We are fixing this gene to make it a functional gene,” says Baasov proudly.