Adrian Krainer, a world-renowned biochemist and molecular geneticist who discovered the world’s first treatment for spinal muscular atrophy (SMA), will receive an honorary doctorate from Tel Aviv University on Thursday.
Krainer, whose New York-based lab studies the mechanisms of RNA splicing, is being honored for “offering hope and enhancing quality of life among sufferers around the world, and [for] his exceptional contribution to understanding the RNA gene-splicing process over the past three decades,” the university said in a statement.
A Jewish Uruguayan-American, Krainer has collaborated with Israeli researchers in various capacities over the past three decades. As the St. Giles Foundation Professor at Cold Spring Harbor Laboratory, he and his team focused on finding a way to treat SMA, a neuromuscular disease that is the leading genetic cause of death in infants.
He told The Jerusalem Post that in SMA, a gene called SMN2 is spliced incorrectly, making it only partially functional. His lab characterized this defect and found a way to correct it using a therapeutic approach. It is possible to stimulate SMN protein production by altering mRNA splicing through the introduction into cells of chemically modified pieces of RNA called antisense oligonucleotides (ASOs).
Following extensive work with ASOs in mouse models of SMA, one such molecule, known as Spinraza, was taken to the clinic. At the end of 2016, it became the first FDA-approved drug to treat SMA, by injection into the fluid surrounding the spinal cord.
The researcher said that since 2016, more than 7,000 patients around the world have benefited from Spinraza. In Israel, the drug was approved and is now covered by the health basket. He said that, “it is an expensive treatment, but is very effective and Israel decided to cover it for all patients.”
One in 10,000 newborns are diagnosed with SMA. Spinraza took 15 years to develop.
Krainer said that “patients being treated [with Spinraza] live longer and can even develop muscle strength.” Otherwise, SMA is a degenerative disease. “Patients can improve over time – and if they are treated early, they can develop normally or close to normally. It is a very striking change over the natural course of the disease.”
HIS LAB is now focusing on using the same approach to study other diseases caused by splicing defects, including familial dysautonomia, a genetic disorder found primarily in Ashkenazi Jews, that affects the development and survival of certain nerve cells.
In addition, his lab has also worked to shed light on the role of splicing proteins in cancer, including characterizing the splicing changes that factor SRSF1 elicits when overexpressed in the context of breast cancer – and discovering how several of these changes contribute to various aspects of cancer progression.
“This is a precision medicine; a very targeted medicine,” Krainer explained of his ground-breaking drug. “It fixes one problem with one gene that underlies this one disease. It cannot be used for other diseases. However, we hope this is an example of an approach, and we can develop drugs for other diseases based on the same principle.”
He said working on cures for rare diseases can be a challenge because such a small number of patients are affected by them, and therefore the research can sometimes struggle for support.
“But for the patients, this research is very important to them,” Krainer said. “A lot of things have to come together to make this happen: basic science, academia, industry collaborators, regulatory agents and then the healthcare system, which has to see the value in getting coverage for patients.
“Everyone has to work together to find these solutions,” he said.
Krainer acknowledged that new multidisciplinary approaches to medicine are making what used to be very difficult problems more manageable, adding that he believes the pharmaceutical industry is trying to adapt to using genomics and other modern techniques.
“They have to be nimble,” he said. “Maybe it’s selfish, but I think there needs to be more investment in basic science. Industry could do more to invest in things from which we won’t immediately reap the benefits; we cannot anticipate where the next discoveries and insights will come from.
“It’s different in every country – who makes the investment and what methods of health coverage people have,” Krainer continued. “But diseases don’t look at these boundaries.”