NEW YORK--(BUSINESS WIRE)--Olatec Therapeutics LLC (Olatec), a leader in the developing class of selective NLRP3 inhibitors, today announced that The Michael J. Fox Foundation for Parkinson’s Research (MJFF) awarded a research grant to evaluate Olatec’s lead molecule, dapansutrile, in preclinical Parkinson’s disease (PD) progression models. These studies are being initiated in collaboration with researchers at the Medical University of Innsbruck in Austria. The studies will assess dapansutrile’s potential effect as an anti-neuroinflammatory agent, and its pharmacokinetics to confirm validated target engagement in certain transgenic and propagation mouse models. The aim of this collaboration is to accelerate the development of a potential therapeutic intervention that may prevent or mitigate the development of PD’s motor and non-motor symptoms.
PD is a complex neurodegenerative disease marked by motor symptoms and in some cases dementia. Loss of neurons in areas that produce dopamine, particularly the substantia nigra, leads to decline in motor performance. Mounting scientific literature suggests a neuroinflammatory process related to aggregation of α-synuclein protein as a potential driver of these changes. A protein found abundantly in the brain, α-synuclein, typically functions in facilitating communications between neurons; however, misfolded α-synuclein can aggregate into intracellular inclusions (Lewy bodies). Age-related accumulation of tangled α-synuclein protein may initiate or run in parallel to an inflammatory cascade resulting in neuron death. As such, significantly, down regulating neuroinflammatory processes may prevent or slow formation of α‑synuclein aggregation.
When asked about the MJFF grant, Charles Dinarello MD, Olatec SAB Chair, said: “The data we have generated using a standard mouse model of Parkinson's disease allow us to advance our findings with the models to be used by Dr. Stefanova. Specifically, our current data reveal that dapansutrile’s reduction in brain levels of pro-inflammatory cytokines, IL-1β and IL‑18, results in significant improved locomotion and lower brain levels of the pathologic α-synuclein. We are very pleased to receive this grant from the MJFF and are hopeful the findings will advance us into a clinical trial with dapansutrile in Parkinson's disease.”
The study, funded by the MJFF grant, will investigate treatment with oral dapansutrile in both an α‑synuclein propagation model in wildtype mice and a transgenic mouse model with upregulated production of full-length human α-synuclein leading to progressive motor deficits. The aim of the study will be to quantify how oral dapansutrile might protect neurons, reduce α-synuclein aggregation and neuroinflammation, and prevent motor deficits. Additionally, the study will evaluate tolerability and pharmacokinetics in the murine system.
Nadia Stefanova MD PhD, the lead investigator on this study, is a professor in the Department of Neurology, Medical University of Innsbruck. Dr. Stefanova is a leader in the field of α-synucleinopathies, which are neurodegenerative diseases characterized by the accumulation of misfolded α-synuclein in brain tissue, including PD, Lewy Body Dementia, and Multiple System Atrophy. Dr. Stefanova’s research focus includes the development of experimental mouse models for therapeutic development as well as the significance of neuroinflammatory responses in disease mechanisms. Commenting on the MJFF grant, Dr. Stefanova said: “We are looking forward to the preclinical investigation of dapansutrile in our α-synuleinopathy models to further advance PD science and investigate the drug’s potential mechanism of action in treating this disease. I am also thrilled to launch our collaboration with Olatec and the lab of Charles Dinarello with the funding support of MJFF, and to work on the preclinical evaluation of dapansutrile for the treatment of PD and related disorders.”
Olatec’s Founder and CEO Damaris Skouras commented: “Olatec is very pleased to be awarded this grant, and to be collaborating with Dr. Stefanova on this important research evaluating dapansutrile in the potential treatment of this debilitating disease with unmet medical need.”
About Parkinson’s disease
Nearly one million Americans are living with PD, and close to 90,000 will be diagnosed this year. Currently, there are no therapeutics that can alter PD disease progression. Patients initially present with complaints of changes in sleep, movement, and speech; worsening physical symptoms are later met with the development of cognitive decline. Medications such as levodopa are palliative, reducing symptom burden but unable to alter disease progression.
Dapansutrile (lab code: OLT1177®) is an investigational small molecule, new chemical entity that specifically binds to and blocks NLRP3 (nucleotide-binding and oligomerization domain [NOD]‑, leucine rich repeat-, pyrin domain-containing 3), the sensor molecule integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of bioactive IL-1β and IL-18 through caspase-1 activation. Dapansutrile has been shown to prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL-1β and IL‑18. NLRP3 is one of the most characterized inflammasome sensors due to its involvement in a wide range of disorders, including sterile inflammation, infections, and rare genetic autoimmune syndromes. Dapansutrile has been well tolerated and shown to improve clinical outcomes in patients with acute gout flare (see The Lancet Rheumatology) and heart failure (see Journal of Cardiovascular Pharmacology). Dapansutrile has also been observed to have anti-inflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models including arthritis, asthma, acute myocardial infarction (AMI), heart failure, contact dermatitis, multiple sclerosis, melanoma, pancreatic and breast cancers, spinal cord injury (SCI), Parkinson’s and Alzheimer’s disease. For a complete list of Olatec’s original publications on dapansutrile in various preclinical and clinical disease areas, please refer to Olatec’s publication page, here.
About Dapansutrile’s Preclinical CNS Research
Dapansutrile is being studied in multiple models of the central nervous system and neuroinflammation, including: Alzheimer’s disease (AD), spinal cord injury (SCI), multiple sclerosis (MS), and Parkinson’s disease (PD). Data to date from these different programs have been or are being published as follows: in the AD studies, data revealed that oral dosing with dapansutrile inhibits pathophysiological inflammatory processes, recovers significant cognitive losses and prevents neuroinflammation in the brains of transgenic mice induced with AD (see publication in PNAS). In models of MS, dapansutrile exerted anti-inflammatory and protective effects on functional and histological outcomes in experimental autoimmune encephalomyelitis mice, when given prophylactically (see publication in Frontier in Immunology). In MPTP models of PD, dapansutrile showed reduced α-synuclein aggregation, preserved dopaminergic neuron survival and reduced IL‑18 levels. In spinal cord injury (SCI) models, dapansutrile protected against neurological deficits and histological evidence of damage (see publication in Experimental Neurology).
About Olatec Therapeutics LLC
Olatec is a privately held, Phase 2/3 clinical-stage biopharmaceutical company developing a platform of oral NLRP3 inhibitors to treat and prevent a broad spectrum of acute and chronic inflammatory diseases known to be mediated by IL-1 (see list of clinical trials to-date, here). In addition to the lead compound, dapansutrile, Olatec’s platform of proprietary compounds includes approximately 60 analogues (OLT Analogues) being screened as viable drug candidates. A portfolio of intellectual property registrations protecting Olatec’s compounds consists of over 130 patents granted, covering dapansutrile and OLT Analogues. Olatec’s drug development team is comprised of experienced management and international experts in translational medicine with unparalleled expertise in inflammation and immunology and has been involved in the discovery and development of first-line inflammation treatments in the market today. For more information, please visit http://www.olatec.com
Disclaimer & Forward-looking Statement
This press release is not an offer to sell and is not soliciting an offer to buy any equity interests in the Company. The information contained herein is being provided for information purposes only. The Company makes no express or implied representation or warranty as to the completeness of this information. Any forward-looking statements contained in this release are based on assumptions made by Olatec at the time this Press Release was prepared. Any forward-looking statement contained in this Press Release is subject to known and unknown risks, uncertainties and other factors that may be materially different from those contemplated in such forward-looking statements. All information with respect to industry data has been obtained from sources believed to be reliable and current, but the accuracy thereof cannot be guaranteed by the Company. Olatec does not undertake any obligation to update or revise the forward-looking statements contained in this Press Release to reflect events or circumstances occurring after the date this Press Release was prepared, or to reflect the occurrence of unanticipated events.