Felix Nitschke, Ph.D.

Dr. Nitschke received his Ph.D. from the University of Potsdam, Germany, in 2013. He performed his doctoral work in the lab of Dr. Martin Steup, an internationally accomplished expert in the field of starch metabolism. This research area is of great relevance to an area of medicine, namely that of glycogen storage disorders. Dr. Nitschke focused his work on the investigation of Lafora disease (LD), where instead of synthesizing exclusively soluble glycogen, insoluble, starch-like glycogen particles accumulate and drive the severe form of progressive childhood-onset epilepsy. He completed his post-doc in the gene therapy lab of Dr. Berge Minassian at The Hospital for Sick Children Research Institute, Toronto, Canada, and is now Assistant Professor at UT Southwestern Medical Center in the Departments of Pediatrics and Biochemistry.

Dr. Nitschke is an expert in carbohydrate research, combining his interest in therapeutic application with a deep understanding of biochemical methodology. He has published several papers in high-ranking peer-reviewed journals and is a frequent speaker at the International Lafora Disease Workshop. In an effort to encourage scientific collaboration and to generally boost understanding of polyglucan metabolism, he published a text book that for the first time integrates enzymology of plant starch and glycogen.

His research led to a paradigm change in the field of glycogen metabolism in regards to Lafora disease pathogenesis. He demonstrated that glycogen hyperphosphorylation is a consequence but not the cause of the disease and that it is the abnormal glycogen structure that is critical for the disease. Furthermore, Dr. Nitschke contributed to the development and testing of a therapeutic approach that is based on a fusion of a starch degrading enzyme and diphtheria toxin (DT), a cell-penetrating protein. He could demonstrate that amylase, fused to a non-toxic form of DT, translocates into the cytosol of human cells, is functional and degrades cytosolic glycogen. Cell-penetrating therapeutic proteins provide a promising platform for the treatment of LD and other diseases where abnormal, starch-like glycogen accumulates.

Dr. Nitschke’s present work is based on two pillars: 1) basic research for a better understanding of glycogen metabolism, especially regarding the mechanisms that ensure glycogen solubility, and 2) establishment of a novel enzyme replacement platform against multiple rare diseases that aims to overcome the caveats of purely viral delivery approaches.

• Cell Metabolism
• Enzyme Replacement
• Glycogen Metabolism (regulation, quality control, related diseases)
• Glycogen Storage Disorders
• Novel Gene Therapy Approaches

Featured Publications

Novel Cross-Correction-Enabled Gene Therapy for CDKL5-Deficiency Disorder.

Nitschke F, Montalbano AP, Neurotherapeutics 2022 Oct

Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency.

Nitschke S, Sullivan MA, Mitra S, Marchioni CR, Lee JPY, Smith BH, Ahonen S, Wu J, Chown EE, Wang P, Petkovic S, Zhao X, DiGiovanni LF, Perri AM, Israelian L, Grossman TR, Kordasiewicz H, Vilaplana F, Iwai K, Nitschke F, Minassian BA, Brain 2022 Jan

An inducible glycogen synthase-1 knockout halts but does not reverse Lafora disease progression in mice.

Nitschke S, Chown EE, Zhao X, Gabrielian S, Petkovic S, Guisso DR, Perri AM, Wang P, Ahonen SJ, Nitschke F, Minassian BA, J Biol Chem 2020 Dec

Sensitive quantification of a-glucans in mouse tissues, cell cultures, and human cerebrospinal fluid.

Nitschke S, Petkovic S, Ahonen S, Minassian BA, Nitschke F, J. Biol. Chem. 2020 Aug

Skeletal Muscle Glycogen Chain Length Correlates with Insolubility in Mouse Models of Polyglucosan-Associated Neurodegenerative Diseases.

Sullivan MA, Nitschke S, Skwara EP, Wang P, Zhao X, Pan XS, Chown EE, Wang T, Perri AM, Lee JPY, Vilaplana F, Minassian BA, Nitschke F, Cell Rep 2019 04 27 5 1334-1344.e6

Lafora disease - from pathogenesis to treatment strategies.

Nitschke F, Ahonen SJ, Nitschke S, Mitra S, Minassian BA, Nat Rev Neurol 2018 10 14 10 606-617

Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease.

Nitschke F, Sullivan MA, Wang P, Zhao X, Chown EE, Perri AM, Israelian L, Juana-López L, Bovolenta P, Rodríguez de Córdoba S, Steup M, Minassian BA, EMBO Mol Med 2017 07 9 7 906-917

Hyperphosphorylation of glucosyl C6 carbons and altered structure of glycogen in the neurodegenerative epilepsy Lafora disease.

Nitschke F, Wang P, Schmieder P, Girard JM, Awrey DE, Wang T, Israelian J, Zhao X, Turnbull J, Heydenreich M, Kleinpeter E, Steup M, Minassian BA, Cell Metab. 2013 May 17 5 756-67

CRISPR-Cas9-mediated editing of starch branching enzymes results in altered starch structure in Brassica napus.

Wang L, Wang Y, Makhmoudova A, Nitschke F, Tetlow IJ, Emes MJ, Plant Physiol 2021 Nov

Targeting Gys1 with AAV-SaCas9 Decreases Pathogenic Polyglucosan Bodies and Neuroinflammation in Adult Polyglucosan Body and Lafora Disease Mouse Models.

Gumusgoz E, Guisso DR, Kasiri S, Wu J, Dear M, Verhalen B, Nitschke S, Mitra S, Nitschke F, Minassian BA, Neurotherapeutics 2021 Apr

 Featured Books

Enzymology of Complex Alpha-Glucans (1st ed.).

Nitschke, F. (Ed.) (2021). CRC Press.

• American Society for Biochemistry and Molecular Biology (2020)
• American Society of Gene and Cell Therapy (2021)
• Association for Glycogen Storage Disease (2020)