Our Science

Detecting Parkinson’s disease early and developing effective treatments are high unmet medical needs that must be addressed simultaneously. Disease detection in its early stages is important to provide maximum therapeutic benefits to patients. At the same time, developing treatments that can slow or halt the progression of the disease is necessary for patients who are diagnosed with Parkinson’s and are currently only offered symptomatic relief. Anacalypsis Therapeutics is focused on a patient-centric approach,  developing biomarkers that can identify Parkinson’s disease in its early stages and creating innovative treatments that can modify the disease’s course. We are focusing on advanced genetically linked targets to achieve this. Our aim is to provide personalized treatments that will cater to the individual needs of patients.

LRRK2

LRRK2 is a protein that is associated with Parkinson’s disease. LRRK2 gene mutations are a major genetic risk factor for the development of Parkinson’s disease. Research into LRRK2 and its role in Parkinson’s disease is ongoing, with the hope of developing new therapeutic strategies to slow or halt the progression of the disease.

Recent studies have suggested that LRRK2 interacts with FADD (Fas-associated death domain) to contribute to the neurodegeneration observed in Parkinson’s disease. FADD is a protein that plays a key role in cell death pathways, including apoptosis and necroptosis, and has also been implicated in the regulation of inflammation.

Our first novel therapeutic AT001 selectively targets the death pathway activated by binding of LRRK2 with FADD, conferring neurodegeneration while leaving the other functions of LRRK2 intact.

BIOMARKERS FOR PRECISION NEUROLOGY

Adopted from Rideout HJ et al., Front Neurosci. 2020 

BIOMARKERS FOR PRECISION NEUROLOGY

Our emphasis on the parallel development of biomarkers extends to optimizing trial design, patient selection, and treatment response monitoring, enabling personalized medicine and identifying subpopulations that may benefit significantly from tailored treatments.

Our research focuses on biomarkers that provide a comprehensive signature and enhance our understanding of how different compounds impact LRRK2 in diverse body tissues. Through our dedicated efforts, we drive the advancement of targeted therapies for LRRK2-related disorders, aiming to improve patient outcomes and pave the way for better treatment options.

Publications

Distinct profiles of LRRK2 activation and Rab GTPase phosphorylation in clinical samples from different PD cohorts

June 2022 

The Future of Targeted Gene-Based Treatment Strategies and Biomarkers in Parkinson's Disease

June 2020

Allosteric Inhibition of Parkinson's-Linked LRRK2 by Constrained Peptides

November 2021

The Current State-of-the Art of LRRK2-Based Biomarker Assay Development in Parkinson's Disease

August 2020

A double-hit in vivo model of GBA viral microRNA-mediated downregulation and human alpha-synuclein overexpression demonstrates nigrostriatal degeneration

February 2022

Doubly Constrained C-terminal of Roc (COR) Domain-Derived Peptides Inhibit Leucine-Rich Repeat Kinase 2 (LRRK2) Dimerization

May 2023

Eileen J. Kennedy

Scientific Advisor

Dr. Eileen J. Kennedy, is a highly accomplished researcher and academic leader in the field of pharmaceutical and biomedical sciences. With a distinguished career spanning academia and cancer research, she currently holds the esteemed positions of Co-Director and Interim Department Head of the UGA Cancer Center at the University of Georgia.

Additionally, she is recognized as the Dr. Samuel C. Benedict Professor, a testament to her expertise and contributions to the field. Dr. Kennedy’s academic journey includes an American Cancer Society Postdoctoral Fellowship at Harvard University and a Ph.D. in Chemistry earned as an American Heart Association Predoctoral Fellow at UCSD. Her research focuses on cancer-related studies, and she has made significant strides in advancing our understanding of the disease.

Throughout her career, Dr. Kennedy has held various academic positions, including Associate Professor with Tenure and Assistant Professor, at the Department of Pharmaceutical and Biomedical Sciences in the College of Pharmacy at the University of Georgia. Her exemplary leadership qualities are evident in her interim roles as Associate Department Head and Assistant Department Head. Dr. Kennedy’s dedication to the scientific community extends beyond her university affiliations, as she serves as an Adjunct Associate Professor in the Departments of Chemistry and Biochemistry and Molecular Biology.

Her extensive experience also encompasses research roles at prestigious institutions such as Harvard University, where she worked as a Research Associate and an American Cancer Society Postdoctoral Fellow.

In addition to her professional accomplishments, Dr. Kennedy is actively involved in disseminating her knowledge through publications and contributions to the scientific community. As a prominent figure in cancer research, she continues to inspire and lead advancements in the field, making her an esteemed academic and researcher in pharmaceutical and biomedical sciences.

R. Jeremy Nichols, PhD

Scientific Advisor

R. Jeremy Nichols, PhD, is a Lead Scientist in St. Jude Children’s Research Hospital. Previously he was a senior research scientist in the Stanford School of Medicine department of pathology. Dr. Nichols was also the Director of Signal Transduction and LRRK2 Biology at the Parkinson’s Institute and Clinical Center in Sunnyvale, CA.

He obtained a BS degree with honors from Austin Peay State University and a PhD from the Medical College of Wisconsin, where he worked in the laboratory of Dr. Paula Traktman. As a postdoctoral fellow with Professor Dario Alessi at the Medical Research Council Protein Phosphorylation Unit in Dundee, Scotland, Dr. Nichols pursued his interest in cellular signaling studying the role of LRRK2 in cells and the genetic causes of Parkinson’s disease (PD).

Dr. Nichols’ research focuses on studying the biochemical reactions and molecules linked to the proteins implicated in PD.

Leonidas Stefanis

Scientific Advisor

Dr. Stefanis obtained his MD from the University of Athens Medical School in 1987. He subsequently obtained his PhD from the same University in 1992, with work related to the molecular basis of thalassemia.

In 1991, he moved to the US, where he trained as Resident in Neurology at Columbia University in New York. In 1995, he embarked on a post-doctoral fellowship in the laboratory of Dr. Lloyd Greene, in the Dept. of Pathology, while in parallel he completed a two-year fellowship on Neurobehaviour, in the Dept. of Neurology at Columbia University.

His work during this time centered on mechanisms of neuronal cell death. In 1998 he was appointed Assistant Professor of Neurology in the Center for Neurodegenerative Diseases in the Dept. of Neurology at Columbia University, position which he held up till 2003. During this time, he focused his interest more on the pathogenesis of neurodegenerative disorders, with an emphasis on Parkinson’s Disease (PD).

In 2003 he moved back to Greece as Researcher Level B at the Biomedical Research Foundation of the Academy of Athens (BRFAA), and set up a laboratory focusing on mechanisms of neurodegeneration, in particular in relation to protein degradation systems, alpha-synuclein and PD.

In 2006 he assumed the appointment of Associate Professor in the University of Athens Medical School, while he continued his work at BRFAA as an affiliated investigator.

In 2012 he was appointed Director of the Second Department of Neurology at «Attikon» Hospital and was elected to the position of Professor of Neurology and Neurobiology at the University of Athens Medical School.

Currently, Dr. Stefanis is investigating various areas of PD pathogenesis, ranging from the bench to the bedside. He is examining the genetic underpinnings of the disease in the Greek population, not only in the rare familial, but also in sporadic cases. He is involved in studies that aim to examine the utility of using alpha-synuclein as a disease biomarker. He is examining pathways of neurotoxicity induced by aberrant alpha-synuclein, with an emphasis on the involvement of protein degradation pathways, such as Chaperone-Mediated Autophagy. He is also investigating the molecular underpinnings of the link of other genetic alterations linked to PD, such as those in UCH-L1, LRRK2 and GBA. He is using a wide array of approaches, ranging from cellular and animal models to studies of patients’ biological material.

Alexandros Papadimitriou

Scientific Advisor

Professor Alexandros Papadimitriou is a highly accomplished and renowned neurologist. With extensive research experience and a strong academic background, he has made significant contributions to the field of neurology.

Currently, he holds the position of Professor and Chairman at the Department of Neurology at the University of Thessalia.

In addition to his academic role, he serves as a Neurologist at the Neurology Department of E. Dynant Hospital.

Throughout his career, Professor Papadimitriou has established fruitful collaborations with prestigious institutions such as Columbia University, Cornell Medical Center, and the University of Milan, among others.

His research work spans various neurological disorders, encompassing epilepsy, stroke, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson’s disease(PD).

Additionally, he has authored numerous publications, including international papers, textbooks, and Greek monographs.

Stelios T. Tzannis

Member Board of Directors

Dr. Tzannis is the Scientific Director of Elpen Lifetech Park. He is also Aeovian’s Founder and has over 25 years of pharmaceutical industry experience from target selection, drug discovery to advanced clinical development.

Prior to Aeovian, he was an EIR & Director of Clinical Sciences at the Buck Institute for Research on Aging; founder & CEO of ARdaix Pharmaceuticals SAS and co-founder & COO of Theralpha SAS. Both of these roles focused on the development of novel therapeutics for the management of acute and chronic pain.

Leading to that, Dr. Tzannis served as Vice President of Pharmaceutical R&D and Executive team member at AcelRx Pharmaceuticals, Inc., Vice President of R&D at iMEDD Inc., Director of R&D and Licensing & Acquisitions at Nektar Therapeutics, and Research Scientist at Alza Corporation.

He holds MS/PhD and Dipl.Eng. degrees in Chemical Engineering from Rensselaer Polytechnic Institute (Troy, NY) and NTUA (Athens, Greece), respectively.

Angeliki Frangou

Member Board of Directors

Angeliki Frangou is a Greek shipowner,chairman, chief executive officer and Director of Navios Maritime Holdings., of Navios Maritime Partners L.P., of Navios Tankers Management Inc. and Navios Maritime Acquisition Corporation.

In 2011, she was named the 50th most powerful businesswoman in Fortune Magazine. Also, she was named as Connecticut Maritime Association’s Commodore for the year 2011.

In 2013, Frangou was mentioned on CNN’s International Leading Women.

In 2014 Frangou was listed 11th in the Lloyd’s List Top 100 Most Influential People in Shipping list.

In 2020, in collaboration with Vangelis Marinakis and ION S.A., they made a donation of 1.5 million euros to the General State Hospital of Nice to help fight the coronavirus. The donation included 14 new, fully equipped intensive care units.

George Nomikos

Member Board of Directors

Pharmaceutical R&D scientist and psychiatry-trained clinician with extensive academic and industry experience in CNS, pain, neuromuscular, and metabolic/neurohormonal therapeutics

Proven track record as a team leader directing large cross-site and cross-functional teams to key advancement decisions in pharmaceutical R&D

Extensive knowledge and expertise in the neurobiology, neuropharmacology, and therapeutics of CNS, metabolic/neurohormonal and orphan/rare and pain disorders

Broad working knowledge of a wide variety of neurochemical, behavioral, physiological, and histochemical techniques, clinical pharmacology, biomarkers, translational and experimental medicine approaches, and clinical trial methodologies

Global clinical science director in charge of early development and registration/pivotal Phase 1-4 clinical trials in CNS, neuromuscular, metabolic/neurohormonal disorders, and pain

Global clinical science lead responsible for development of internal documents and major contributor to preparation of regulatory documents, and other external documents and presentations

Global medical lead for strategy, planning, execution, alliance and joint clinical development team representation, cross-functional team guidance, and regulatory and KOL interactions in programs from early development through regulatory approval and LCM

Clinical science lead for early-stage projects from candidate selection to IND, working cross-functionally with global teams for the development of integrated global developmental strategy, IND preparation, CDP development, Phase 1 and POC studies

Oversee trial conduct and operations, evaluate, select, and manage CROs, coordinate and support statistical analyses, investigator meetings, scientific and clinical advisory boards, FDA/EMA meetings, medical monitoring, and medical affairs strategy, liaise with commercial and market access groups, engage KOLs, support health outcomes teams, train MSLs, sales force and speakers for educational and promotional purposes, and evaluate investigator-initiated study proposals

Clinical science lead for global target hunting initiatives, in-licensing and due-diligence evaluations

Cofounder, board member and advisor of start-up biotech companies

Hardy J. Rideout

CSO, Co-Founder

Hardy J. Rideout, PhD, received his undergraduate degree from Wilfrid Laurier University in Waterloo, Ontario, Canada, and completed his PhD in Anatomy & Neurobiology from Dalhousie University in Halifax, Nova Scotia, Canada. He completed a post-doctoral fellowship in the laboratory of Dr. Leonidas Stefanis at Columbia University in New York, studying the role of dysfunction of protein degradation systems on neuronal death and inclusion body formation in cellular models of Parkinson’s disease. He then joined the lab of Dr. William Dauer at Columbia as an associate research scientist where he began his study of the pathogenic mechanisms of LRRK2. In 2009, he joined the Neurodegenerative Diseases Research Group at the Biomedical Research Foundation of the Academy of Athens in Greece, where he continues his work focusing on the links between altered LRRK2 localization and signaling, and the activation of neuronal death pathways.

Alexia V. Polissidis

CEO, Co-Founder

Alexia V. Polissidis holds a BSc Honors Pharmacology degree from the University of Alberta, Canada and a PhD in Psychopharmacology from the Medical School, University of Athens. She is an Assistant Professor of Pharmacology at The American College of Greece and an independently-funded Junior Research Team Leader at the Center for Clinical, Experimental Surgery, and Translational Research at the Biomedical Research Foundation of the Academy of Athens, where she also established in 2011 the NeuroBehavior Rodent Phenotyping Facility. She has a background in psychopharmacology and translational neuroscience with expertise in preclinical drug screening, cannabinoid pharmacology and transgenic and viral rodent models of neurodegenerative and neuropsychiatric diseases. Alexia has received 2 grants and 6 awards for her research, published 38 peer-reviewed papers, and co-authored two book chapters. Alexia currently serves as a member of the Governing Council of the Hellenic Society for Neuroscience. She was a member of the first National Committee for Medicinal Cannabis Products and an external advisor for the European Medicines Agency Expert for the Committee for Medicinal Products for Human Use.