12:01 PM
 | 
Nov 16, 2017
 |  BC Innovations  |  Tools & Techniques

Yeast against aggregation

How yeast could provide new targets for neurodegenerative diseases

In drug discovery for neurodegenerative diseases, the emphasis is on finding better models of neuronal systems that recapitulate synapses, neuroinflammation and the pathological accumulation of toxic aggregates. Yumanity Therapeutics LLC and a handful of academic labs are taking the counterintuitive strategy of searching for clues in yeast -- trading the organism’s lack of nervous system for its well-characterized genetics and ease of manipulation.

The idea is rooted in the fact that many cellular systems are highly conserved between yeast and humans, and the belief that the biology behind aggregate formation and its consequences will be faithfully represented in the lower organisms.

Advocates think the fungi will offer a faster path to discovering new targets and compounds than assays in mammalian cells, as well as hits more likely to translate to humans than those produced via in vitro screens.

Yumanity was launched in 2014 by its CEO, biotech veteran Tony Coles, based on the work of its late co-founder, Susan Lindquist, a professor at the Massachusetts Institute of Technology (MIT) who had built a suite of yeast-based tools for finding targets related to protein misfolding. The company raised a $45 million series A round in February 2016, led by Fidelity Management & Research Co. Lindquist passed away late last year.

Yumanity’s platform takes advantage of the relative simplicity of the yeast genome and the high conservation of molecular pathways between yeast and mammals to screen for compounds that can keep cells alive in the presence of toxic aggregates.

“Yeast is the best studied organism on the planet by far,” Yumanity CSO Kenneth Rhodes told BioCentury. “All that wealth of data helps you interpret the outcome of target identification experiments in a way that you just can’t approach in mammalian cells.”

But apart from Yumanity, few companies are using yeast for neurology drug discovery. It’s academics who have been pushing the system forward, he said.

Last month, a Cell study from Boston University and MIT demonstrated how yeast can be used to find ways of intervening in the aggregation process directly.

“Previous to this, there were no good cell-based methods for screening against protein aggregation.”

Ahmad Khalil, Boston University

Although the organisms have neither neurons, synapses nor immune systems -- which Rhodes believes underlies the limited interest in industry -- he considers those limitations “minor” compared with the “overall power of the system and the tremendous conservation of the biology.”

Rhodes...

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