against multiple neurological disorders. “We’re not saying we’re going to develop one compound and cure all diseases,” Kelly says. “I think it’s still a notion of one compound that affects a signaling pathway that regulates the proteostasis network. We’re still looking for drugs with a high degree of specificity, and we’ll do a clinical trial in one disease.”
This whole idea of the proteostasis network is the sort of thing you could try to draw in some crazy quilt PowerPoint slide, but it wouldn’t do much good for the viewer. It’s complicated. And the whole notion of the proteostasis network is still a pretty new concept for scientists, Kelly says. The world of protein biology used to be divided into different camps that focused on molecular chaperones, proteasomes, and other specific kinds of proteins and “we all went to separate meetings,” Kelly says. But in the last few years more and more scientists have come around to the idea of studying their proteins in the context of networks. “They all play together,” as Kelly says.
The Proteostasis founders have some early experimental data which I alluded to back in February. Some of the work being done now is testing certain nodes on the proteostasis network in animal models, and matching those results up against cells grown in lab dishes from patients with a certain disease. The researchers are looking for any alteration of the protein network, and seeing if that correlates with any outward appearance of disease improvement in animals.
If the proteostasis network can be established as playing an important role in neurodegenerative diseases, then Proteostasis might have discovered more than just a promising new drug target. Scientists could start looking at the perturbations in the protein network that could be an early sign of disease in the works, long before symptoms like the forgetfulness of Alzheimer’s start to appear. The company hopes it will be able to use these as novel biomarkers that might be able to tell whether a patient is in the early or late stages of Alzheimer’s, and possibly whether they are likely to respond to a certain treatment or not.
Kelly has been around the block as an entrepreneur before, having co-founded Cambridge, MA-based FoldRx Pharmaceuticals. Tantalizing as the concepts at Proteostasis are in its early days, I asked him what makes this idea ready to leave academia and become the basis of a company.
“People don’t invest money if they think it’s basic science,” Kelly says. “I think we have enough evidence that we can show with chemical matter that we can connect a molecule to a pathway to a disease, which is what got people excited that this is real. Now we need to really make drugs.”
