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EDINBURGH, Scotland--( BUSINESS WIRE )--Lario Therapeutics (‘Lario’, or ‘the Company’), a biopharmaceutical company developing first-in-class precision medicines for epileptic and neurological disorders, today announced it has been awarded a $6 million USD grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). The programme is in collaboration with the Oxford Parkinson’s Disease Centre, which will also be delivering key science as part of the grant. The grant will be used to fund Lario’s preclinical programme investigating selective CaV2.3 calcium channel inhibition as a novel and disease-modifying approach for treatment of Parkinson’s disease. There is extensive literature linking calcium channels to pathology of the disease, and it has been demonstrated in preclinical experimental studies that the deletion of CaV2.3 can have a protective effect against Parkinson’s disease progression. Lario is partnering with Professor Richard Wade-Martins and the Oxford Parkinson’s Disease Centre (OPDC) for the study, for the evaluation of Lario compounds in state-of-the-art patient-derived stem cell models of Parkinson’s disease. Parkinson’s disease is a progressive neurodegenerative disorder occurring when brain cells that make dopamine, which coordinates movement, stop working or die. Symptoms are lifelong and worsen over time, including motor disfunction, such as tremor, slowness, stiffness, walking and balance problems, as well as problems such as depression and memory problems. More than 10 million people worldwide are estimated to be living with Parkinson’s, with no current cure. Tom Otis, Ph.D., Professor of Neuroscience UCL and Chief Scientific Officer of Lario Therapeutics, said: “ We are grateful to MJFF for their funding support for Lario’s efforts to test and develop a potential new therapy designed to prevent the loss of neurons that causes Parkinson’s disease. If our research is successful, this will represent an important new treatment option for patients.” “This significant funding from The Michael J. Fox Foundation will aid the work out of our therapeutic pipeline and the work we have achieved so far in advancing research in the field. We would like to thank the MJFF team for their support,” added Henning Steinhagen, Ph.D., Co-Founder and CEO of Lario Therapeutics. “This grant will help drive our ambition to progress our Cav2.3 program swiftly towards the clinic, to provide a new, effective treatment option for people with Parkinson’s disease.” “ MJFF is dedicated to funding innovative research, such as the work done at Lario Therapeutics, to develop a pipeline of novel therapies that can improve the lives of people with Parkinson’s disease ,” said Gaia Skibinski, Ph.D., director of research programs at MJFF . “ We look forward to seeing the results of Lario’s research on CaV2.3 as a novel disease-modifying approach for Parkinson’s .” Richard Wade-Martins, MA, DPhil, Professor of Molecular Neuroscience, University of Oxford, and head of the Oxford Parkinson’s Disease Centre, said: “ I am excited to partner with the team at Lario Therapeutics – having grant funding from MJFF is a testament to the impact this study aims to bring to patients. Our research centre works to understand the development of Parkinson’s, with the ultimate aim of targeting the molecular mechanisms of disease, to prevent disease onset or to delay progression. We see great potential in the CaV2.3 programme and are very happy to collaborate to study patient stem cell-derived neuronal models as part of the research.” For more information about Lario Therapeutics' pipeline please visit https://www.lariotx.com/pipeline .

Researchers have identified a potential treatment target for a genetic type of epilepsy.   Researchers at the Francis Crick Institute, UCL and MSD have identified a potential treatment target for a genetic type of epilepsy. Developmental and epileptic encephalopathies are rare types of epilepsy which start in early childhood. One of the most common types of genetic epilepsy, CDKL5 deficiency disorder (CDD), causes seizures and impaired development. Children are currently treated with generic antiepileptic drugs, as there aren't yet any disease-targeting medications for this disorder. CDD involves losing the function of a gene producing the CDKL5 enzyme, which phosphorylates proteins, meaning it adds an extra phosphate molecule to alter their function. Until now, researchers have not been sure how genetic mutations in CDKL5 cause CDD. Through their research, published today in Nature Communications, the researchers examined mice which lacked the Cdkl5 gene, and used a technique called phosphoproteomics to scan for proteins which are a target for the CDKL5 enzyme. They identified a calcium channel, Cav2.3, as a target. Cav2.3 allows calcium to enter nerve cells, exciting the cell and allowing it to pass on electrical signals. This is needed for the nervous system to function properly, but too much calcium coming into cells can result in overexcitability and seizures. The researchers then recorded from the calcium channels to see what was happening when they were not being phosphorylated by CDKL5. The channels were able to open, but were taking a lot longer to close, leading to larger and more prolonged currents flowing through them. This implies that CDKL5 is needed to limit calcium entry into cells. The researchers also used nerve cells derived from stem cells taken from people with CDD, again observing that phosphorylation of Cav2.3 was reduced. This suggests that Cav2.3 function is potentially altered in humans as well as mice. Mutations in Cav2.3 that enhance channel activity are already known to cause severe early onset epilepsy in a related condition called DEE69, which shares a lot of the same symptoms of CDD. These results suggest that Cav2.3 overactivity is a common feature of both disorders, and that inhibiting Cav2.3 could help with symptoms like seizures. Sila Ultanir, Senior Group Leader of the Kinases and Brain Development Laboratory at the Crick, said: "At the moment, there's a clear need for drugs which specifically target the biological nature of CDD. We've made a molecular link between CDKL5 and Cav2.3, mutations in which produce similar disorders. Inhibiting Cav2.3 could be a route for trials of future targeted treatments." Marisol Sampedro-Castañeda, postdoctoral researcher at the Crick, and first author, said: "Our research highlights for the first time a CDKL5 target with a link to neuronal excitability. There's scattered evidence that this calcium channel could be involved in other types of epilepsy too, so we believe that Cav2.3 inhibitors could eventually be tested more widely. "Our findings have implications for a large group of people, from the families affected by these conditions to researchers working in the rare epilepsy field." This research was funded by MSD and the Loulou Foundation, a private foundation dedicated to the development of therapeutics and eventual cures for CDD. Jill Richardson, Executive Director and Head of Neuroscience Biology at MSD, said: "MSD is proud of this innovative research resulting from a collaboration with researchers at the Crick and UCL. We have collectively furthered our scientific understanding of the biological targets associated with the aetiologies of Developmental Epileptic Encephalopathies -- an understanding we hope will contribute toward scientific progress in this important area of high, unmet medical need." The researchers are now working with Lario Therapeutics, a recently launched biotech company which is seeking to develop first-in-class CaV2.3 inhibitors as precision medicines to treat CDD and related neurodevelopmental syndromes.

“CDLK5 Forum Award for Excellence - Company Making a Difference 2023 Pre-clinical” presented by the Loulou Foundation at the CDKL5 Forum, 6th-7th November in London First-in-class ion channel inhibitors show promise as anti-seizure therapeutics for multiple treatment-resistant epilepsy subtypes CaV2.3 identified as a novel target for CDKL5 Deficiency Disorder Lario Therapeutics is a spin-out company from Epidarex Exeed, the therapeutic discovery engine of Epidarex Capital EDINBURGH, Scotland--(BUSINESS WIRE)-- Lario Therapeutics (‘Lario Tx’, or ‘the Company’), a biopharmaceutical company developing first-in-class precision medicines that are targeting disease-modifying treatments for severe neurological disorders, has received the “CDLK5 Forum Award for Excellence - Company Making a Difference 2023 Pre-clinical” from the Loulou Foundation at the annual CDKL5 Forum. The award is in recognition of its development of a validated, precision medicine approach in genetic epilepsies. Lario Tx’s first-in-class, orally active, CNS-penetrant CaV2.3 ion channel inhibitors hold promise as novel anti-seizure therapeutics for multiple epilepsy subtypes, including CDKL5 Deficiency Disorder. The CDKL5 Forum, established by the Loulou Foundation, is the largest annual conference on CDKL5 Deficiency Disorder (CDD). CDD is the most prevalent form of genetic Developmental Epileptic Encephalopathy (DEE), affecting approximately 1:40K live births. Caused by loss-of-function mutations in the CDKL5 protein kinase expressed in the brain, the rare neurological disease leads to seizures, developmental delay and severe intellectual disability in most patients. The leading hypothesis is that CDKL5 regulates the function of the CaV2.3 channel, which can explain the devastating seizures characteristic of the disorder. CaV2.3 is now being investigated as a key target for CDD and CaV2.3 inhibitors hold great promise as a precision medicine approach. Henning Steinhagen, Ph.D., Co-Founder and CEO of Lario Therapeutics, commented: “We are honored and thank the Loulou Foundation for their recognition of our approach which we hope will have a positive impact on patients affected by CDKL5 Deficiency Disorder. Our target, CaV2.3, represents one of the few newly validated precision medicine approaches in neurology and has a significant potential in severe epileptic conditions and other neurological disorders including Parkinson’s disease. We are planning to progress our therapeutic programs swiftly towards IND and beyond supported by our partners and investors.” Dan Lavery, Ph.D., CSO of the Loulou Foundation, stated: “The CDKL5 Forum ‘Company Making a Difference Award (Pre-clinical)’ recognises the industry partner who has demonstrated the greatest commitment to pre-clinical therapeutic development for CDD over the past year. At the CDKL5 Forum 2023, the Loulou Foundation is pleased to recognise the team at Lario Therapeutics, a dynamic group of experienced scientists who are developing a novel therapeutic for our patients living with CDD. The Lario team has shown amazing dedication and engagement with our community, and we are excited to have them join our CDKL5 community as they advance their CaV2.3 pre-clinical development program.” Ana Mingorance, Ph.D., CDO of the Loulou Foundation, added: "One of the major discoveries about CDD last year was that CaV2.3 is a key target for CDKL5, which is deregulated in the absence of CDKL5. This means that CaV2.3 inhibitors hold promise as a precision medicine approach to treat CDD.” Sinclair Dunlop, Investor Director, Lario Therapeutics, said: “This is an exciting time for Lario Therapeutics, and Epidarex Capital is pleased to have supported Henning and the team to this significant point. The Company’s approach to developing novel disease-modifying precision medicines for the management of severe neurological disorders is potentially transformative, places Lario in a unique position to address unmet clinical needs, and represents a significant market opportunity.” Lario Tx was founded in 2021 as a spin-out from Epidarex Exeed (epidarex-exeed.com), the therapeutic discovery engine of Epidarex Capital, with seed investment from Epidarex Capital and Axxam which transferred its participation into Golgi Neurosciences. The Company is rapidly advancing, led by Dr Henning Steinhagen, Co-founder and CEO, together with a highly motivated and experienced team. For more information about Lario Therapeutics please visit lariotx.com. View source version on businesswire.com: Contacts Zyme Communications Katie Odgaard Tel: +44(0)7787 502 947 Email: katie.odgaard@zymecommunications.com Source: Lario Therapeutics View this news release online at: