CADRe Framework
Dr. Coughlin served as part of the Consent & Disclosure Recommendations (CADRe) workgroup in the ClinGen resource.
- 🏥 First clinical studies using lysine-reduction therapies (LRT)
- 🏥 Demonstration that early treatment with LRT improves IQ
- 🏥 Consensus guidlines for diagnosis and treatment
- 🏥 New clinical insights from the International PDE Registry
Precision Medicine
We aim to understand the underlying disease mechansim of PDE-ALDH7A1 with a focus on biochemistry. This work led us to identify a new metabolite within lysine metabolism (6-oxo-pipecolate) that we later applied to newborn screening. Our current research focuses on impact of global metabolic dysfunction and the impact of α-AASA dehydrogenase deficiency. This work is funded by NIH/NICHD and the CurePDE Foundation.
- 🧬 Human samples to identify and evalute novel biomakers
- 🧬 Animal models to elucidate the impact of metabolic dysfunction
- 🧬 Functional studies focused on unique genetic variants
- 🧬 Translation of research results to clinical partners
Novel Genetic Therapies
Although lysine reduction therapies improve clinical outcomes, nutritional based treatments are diffiuclt and associted with a negative impact on quality of life. We collaborate with the CHARLIE consoritum, other scientists, biotech, and pharmaceutical partners to evalute genetic based therapies for PDE-ALDH7A1. This includes several approaches to substrate reduction therapy. This work is funded by philanthropic donations and the CurePDE Foundation.
- 💊 Zebrafish and mouse models allow us to evalute new treatments
- 💊 Leveraging disease expertise to ensure meaningful outcomes
- 💊 Enagement with stakeholders to ensure patinet-first approaches
- 💊 Translational approches to move quickly from lab to the clinic
Below are select publications that highlight our work on PDE-ALDH7A1. Our other mansucripts on PDE-ALDH7A1 are avaiable in the publication section of this website and on public databases such as Google Scholar.
van Karnebeek CDM, Galius-Durner V, Engelke UF, Seisenberger C, Marschall S, Dragano NRV, da Silva-Buttkus P, Leuchtenberger S, Fuchs H, de Angelis MH, Wevers R, Coughlin CR 2nd, Lefeber DJ. New treatment for PDE-ALDH7A1: First proof-of-principle of upstream enzyme inhibition in the mouse. Brain Comm. 2025 Oct 14;7(6):fcaf397 Link
Pauly K, Woontner M. Abdenur JE, Chaudhari BP, Gosselin R, Kripps KA, Thomas JA, Wempe MF, Gospe SM Jr, Coughlin CR 2nd. Feasibility of newborn screening for pyridoxine-dependent epilepsy. Mol Genet Metab. 2025 Jan; 144(1):109002. Link
Coughlin CR 2nd, Tseng, LA, Bok LA, Hartmann H, Footitt E, Striano P, Tabarki BM, Lunsing RJ, Stockler-Ipsiroglu S, Gordon S, Van Hove LK, Abdenur JE, Boyer M, Longo N, Andrews A, Janssen MCH, van Wegberg A, Prasad C, Prasad AN, Lamb MM, Wijburg FA, Gospe SM Jr, van Karnebeek C, International PDE Consortium. Association between lysine reduction therapies and cognitive outcomes in patients with pyridoxine-dependent epilepsy. Neurology. 2022 Aug 25:99(23):e2627-36. Link
Coughlin CR 2nd, Tseng LA*, Abdenur JE, Ashmore C, Boemer F, Bok LA, Boyer M, Buhas D, Clayton PT, Das A, Dekker H, Evangeliou A, Feillet F, Footitt EJ, Gospe SM Jr, Hartman H, Kara M, Kristensen E, Lee J, Lilje R, Longo N, Lunsing RJ, Pearl PL, Piazzon F, Plecko B, Saini AG, Santra S, Sjarif DR, Stockler-Ipsiroglu S, Striano P, Van Hove JLK, Verhoeven-Duif NM, Wijburg FA, Zuberi SM, van Karnebeek CDM†. Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis. 2021 Jan;44(1):178-192. Link
Wempe MF, Kumar A, Kumar V, Choi YJ, Swanson MA, Friederich MW., Hyland K, Yue WW, Van Hove JLK, Coughlin CR 2nd. Identification of a novel biomarker for pyridoxine-dependent epilepsy: Implications for newborn screening. J Inherit Metab Dis. 2019 May;42(3):565-574. Link
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