Teva Pharmaceuticals (Ireland)

In the past years, the demand for critical raw materials, which are needed for green technologies like electric cars, solar panels, and electro-mobility, has rapidly increased. Whilst recycling can provide an increasing portion of these elements, recycling alone cannot meet the estimated demand. This implies that further mining will be required if the EU is to meet its climate goals. Within the project VECTOR, we are developing and testing a new geophysical technique, which is passive and non-disruptive, to image the Earth’s subsurface and structural layers. This method, known as ambient noise tomography, uses signals present in the survey area, such as noise from wind or traffic, to derive a 3D subsurface model. We test the usefulness of this method in Collinstown in the Irish Midlands, known for its significant zinc deposits. Although the resolution of the passive techniques is lower than that of the active seismic methods, we can image layers like the Pale Beds, which are the most prospective host rocks for base metal mineralization, and their depths agree well with those derived from the active 2D methods. This demonstrates that passive seismic surveys can complement active methods, opening new exploration strategies. • Tested passive seismic methods in a mineral exploration context in Ireland. • Successfully imaged geological units likely to host base metal mineralization. • Good agreement with layer depths derived from 2D active reflection seismics. • Passive, low-cost seismic surveys can complement active, expensive methods.

Dysregulation of the kynurenine pathway (KP) leads to imbalances in neuroactive metabolites associated with the pathogenesis of several neurodegenerative disorders, including Huntington’s disease (HD). Inhibition of the enzyme kynurenine 3-monooxygenase (KMO) in the KP normalises these metabolic imbalances and ameliorates neurodegeneration and related phenotypes in several neurodegenerative disease models. KMO is thus a promising candidate drug target for these disorders, but known inhibitors are not brain permeable. Here, 19 new KMO inhibitors have been identified. One of these (1) is neuroprotective in a Drosophila HD model but is minimally brain penetrant in mice. The prodrug variant (1b) crosses the blood–brain barrier, releases 1 in the brain, thereby lowering levels of 3-hydroxykynurenine, a toxic KP metabolite linked to neurodegeneration. Prodrug 1b will advance development of targeted therapies against multiple neurodegenerative and neuroinflammatory diseases in which KP likely plays a role, including HD, Alzheimer’s disease, and Parkinson’s disease.