CSO: Dr. Vladislav Krupalnik
Epeius pharma is a cell and gene therapy company developing next generation biological vehicles for delivery of therapeutic proteins into the central nervous system (CNS). Efficient and predictable therapeutics delivery is particularly challenging in neurological diseases due to the blood-brain barrier (BBB), which tightly regulates the transport of molecules to the brain, and blocks the transport of most large, charged and hydrophilic molecules, which are common features of therapeutic agents. The lack of efficient CNS delivery methods limits protein replacement therapy and remains to be one of the greatest unmet needs for neurological disorders treatment.
While the problems of delivery across the BBB and into cells present crippling challenges for drug delivery, some organisms have independently evolved to breach the BBB and secrete proteins to their host’s cells. A striking example is Toxoplasma gondii, a highly prevalent intracellular protozoan parasite, which infects all warm-blooded organisms. It is estimated that 30% of human population have antibodies for Toxoplasma gondii, which indicates they were exposed for Toxoplasma in their life span. Upon entry into the human body, T. gondii actively migrates to the brain and passes the blood brain barrier (BBB). Most importantly, throughout the infection, T. gondii secrets effector proteins into the host neuron cells and into the extracellular brain environment.
Multiple neurodevelopmental and neurological pathologies could benefit from direct neuron protein replacement treatments. Epeius-Pharma’s platform could allow for an effective and scalable strategy for disease medication in these pathologies. Our first target indication will be Rett Syndrome.
Rett Syndrome is a debilitating neurological disorder that arises primarily from de novo mutations in the X-linked MECP2 gene and affects approximately 1 in 10,000 females worldwide. It is characterized by apparently normal early development followed by profound neurologic regression around 1-2 years of age and often result in shorter life span of patients. Although Rett Syndrome was shown to be reversible by the re-activation or supplementation of MECP2, the lack of robust methods for the delivery of proteins, and especially delivery to the CNS, prevented the application of protein-based therapies for Rett Syndrome. Although there are efforts to develop gene therapy for delivery of an intact MECP2 gene to neurons in the CNS, they have been facing challenges related to packaging limitations of the viral vectors, limited brain transduction efficiency and toxicity. We will use our novel CNS delivery platform to introduce MECP2 to MECP2 deficient neurons of Rett patients.
Vladislav Krupalnik, PhD | CSO
Dr. Krupalnik holds a PhD from the Weizmann institute of science (Rehovot, Israel). He has a vast expertise in development of molecular biology, stem cells, genomics and disease modeling systems. He is a former VP R&D of a clinical diagnostic and genomics company, managing the molecular and bioinformatic development.
Michal Reichenstein, PhD | Scientist
Dr. Reichenstein holds a PhD from Tel Aviv University in the field of biochemistry and neurobiology. Her work focused on elucidating the role of Abelson non-receptor tyrosine kinases in regulation of synaptic activity and plasticity, acquiring skills in sophisticated electrophysiological techniques, as well as vast knowledge and expertise in molecular biology and biochemistry.
Neta Rosenzweig , PhD | Scientist
Dr. Rosenzweig holds a PhD from the Weizmann institute of science (Rehovot, Israel). She has a vast expertise in neuroimmunology and behavioral neuroscience. Her work focused on elucidating the role of peripheral immune cells in Alzheimer’s disease and dementia, demonstrating that transient reduction in systemic immunosuppression, rather than augmenting immunosuppression, has a beneficial effect on disease pathology in murine models.
Shahar Bracha, PhD | Scientific Advisor and Co-inventor
Shahar completed her Ph.D. in Neuroscience in Tel Aviv University under the supervision of Prof. Oded Rechavi during which she developed the technology of T. gondii-based intracellular protein vectors used in Epeius Pharma. She led the project both in Tel Aviv University and in the Wellcome Center for Integrative Parasitology (WCIP) at the University of Glasgow, through collaboration and under co-supervision of Dr. Lilach Sheiner.
Prof. Oded Rechavi, PhD | Co-inventor
PI, Head of the Rechavi lab at Tel Aviv University. Using nematodes, Prof. Rechavi showed that starvation and viral infections produce small RNA-mediated transgenerational effects that prepare the progeny for the challenges that the parents met (Cell 2011 and 2014). Recently, the Rechavi lab discovered rules and genes that determine which heritable epigenetic responses would be inherited to the progeny, and for how long each response would last (Cell 2016, Current Biology 2017, eLife 2019, Current Biology 2019, Cell 2019). Aside from his affiliations in Tel Aviv University, Oded is also a Senior Research Associate in Van Leer Jerusalem Institute, and is a team member in the Allen Discovery center, the Paul G. Allen Frontiers group, in Tufts University, Boston.
Dr. Lilach Sheiner, PhD | Co-inventor
PI, Head of the Sheiner lab at the WCIP at the university of Glasgow. Internationally recognized expert in cell biology and genetic manipulation of T. gondii. Developed widely used tools for Toxoplasma engineering. Leading projects on identification of drug targets and drug development for treatment of Toxoplasmosis. Royal Society of Edinburgh Personal Research Fellow, co-founder and co-director of the annual Middle East Biology of Parasitism Advanced Course.