4:57 PM
Jul 26, 2018
 |  BC Innovations  |  Targets & Mechanisms

PureTech plumbs the brain

Why PureTech is targeting brain lymphatics to treat neurodegeneration

PureTech Health plc is backing a new way of thinking about Alzheimer’s disease that positions it primarily as a problem of poor drainage, building on the recent discovery of lymphatic vessels in the brain by Jonathan Kipnis at the University of Virginia.

The company licensed the IP from UVA and will collaborate with the academic group to develop modulators of brain lymphatic vessels. Terms of the deal are undisclosed.

The findings add a mechanism to how β-amyloid and other proteins are cleared from the brain, which also occurs via transfer across the blood-brain barrier to the bloodstream or enzymatic breakdown inside the brain.

In 2015, Kipnis overturned a long-standing dogma in neuroscience by showing that the meningeal membranes around the brain contain a network of lymphatic vessels. Before then, the brain was thought to be the only organ lacking the vessels. Results were published in Nature.

The outstanding questions have been whether the brain’s lymph vessels drain macromolecules from its interstitial fluid, and if so, whether their dysfunction might contribute to neurodegenerative disorders by causing toxic molecules to build up.

“The view has been Alzheimer’s is a disease of protein homeostasis. The problem could be a drainage issue rather than some intrinsic parenchyma problem.”

Joseph Bolen, PureTech

In a Nature paper published July 25, Kipnis’ group shows both are likely true, as ablation of the vessels led to a buildup of β-amyloid in the meninges and brains of mice. Moreover, injection of the growth factor VEGF-C into the cerebral ventricles reversed age-related shrinkage of lymphatic vessels and cognitive decline.

PureTech CSO Joseph Bolen told BioCentury the findings could fundamentally shift the field’s thinking on the pathogenesis of AD.

“The view has been Alzheimer’s is a disease of protein homeostasis. The problem could be a drainage issue rather than some intrinsic parenchyma problem,” said Bolen.

PureTech aims to be an early mover in the brain lymphatics space, which it highlighted at its inaugural Brain, Immune, Gut (BIG) Axis Summit in January (see “PureTech’s Lymphatic Leap”).

Instead of its typical strategy of spinning a new project into a subsidiary, PureTech is developing its lymphatics program through its internal research division Ariya.

Bolen said the lymphatics program differs from others it has invested in because it is at an earlier stage and larger in scope. Ariya is sourcing a suite of technologies from different places and building a platform for a wide variety of diseases, both inside and outside the brain.

“The internal Ariya division marks our desire to invest in very early research. We think...

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