Molecular imaging to diagnose, monitor and treat disease
From IMFA: By Avigayil Kadesh
Israeli biotech company Aposense offers a futuristic way of diagnosing, monitoring and treating disease through molecules designed to detect cell death (apoptosis). While apoptosis is a universal process in cell biology, it plays a role in most medical disorders. Targeting cells undergoing apoptosis, for imaging or delivering therapy, can therefore have broad clinical applications.
Aposense's patented small molecular probes selectively identify and accumulate within dying cells. They act as an imaging agent to show areas of disease or to provide a picture of the effects of treatment on cancerous cells only hours or days afterward, without any need for tissue samples.
This nearly instant molecular imaging is a vast improvement over conventional anatomical imaging, which cannot detect disease or demonstrate the effects of treatment until months later. Aposense CEO Yoram Ashery says that clinical trials at 12 major American medical centers are currently testing Aposense imaging capabilities in 90 patients with various kinds of malignant tumors. Results should be ready to present to the US Food and Drug Administration late this year.
Direct drug delivery spares healthy cells
"By allowing clinicians to know early if a treatment is working, we are enabling a new paradigm of tailoring treatments to the patients, and an important step in materializing the vision of personalized medicine," he says.
Imaging is not the only promising use for Aposense molecular solutions. They also can deliver drugs directly to apoptotic cells and tissues without harming healthy cells. Aposense and Israel's Teva Pharmaceuticals are progressing toward designing such a targeted drug therapy for cancer, which would offer a significant advance in chemotherapy. However, the potential applications go way beyond oncology, into neurology and cardiology.
"With our platform for targeting apoptosis, there are many diseases we can be effective against, using our rationally designed probes to carry the medication to the target," says Ashery. "We want to put out four or five new candidates per year."
Petah Tikva-based Aposense, founded by neurologist Ilan Ziv in 1997 and chaired by former Teva CEO Eli Hurvitz, was privately held until its initial public offering on the Tel Aviv Stock Exchange in June. Each of its 30 staff chemists, molecular biologists, bioinformatics specialists, pharmacists, physicians and clinicians oversees a single project with outside collaborators, such as Teva. A clinical team of five travels frequently to the US to monitor hospital trials.
"Rational drug design"
Just as the molecular approach to imaging and drug delivery is novel, so is the mode of developing it, Ashery explains. Traditionally, pharmaceuticals are derived through a process of "discovery," involving lots of trial and error until the most effective formula is found. However, that method does not allow the developers to understand exactly why it works or under what conditions it might stop working, Ashery notes.
"The more advanced development approach is 'rational drug design,' based on studying the targets from every biochemical aspect and using computational technologies to design a structure optimal for that target," he says. "We've taken that path of rational design, which takes longer because you're building your molecules atom by atom, like Legos. But once you've optimized it, you know the specific role of each and every atom, and then you can also modify it as necessary for particular purposes."
Pharmaceutical powerhouses including Roche in Switzerland and GlaxoSmithKline in the United Kingdom recently signed agreements with Aposense allowing them to use the specially formulated molecules in drug-development studies. "In return, we get the data from those tests," says Ashery. "It's a win-win situation."
Possibilities for expanding the use of Aposense molecules in imaging are also being explored in the laboratories of US academic institutions affiliated with clinical test sites.