start-up receives €10 million in seed funding for 1st-in-class therapy for ALS | Fundamental pharmaceutical therapy aims to protect nerve cells from disease

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FundaMental Pharma, a preclinical neuroscience spin-out company from the University of Heidelberg, Germany, has just been launched with seed funding of €10 million and a goal to develop new treatments for amyotrophic lateral sclerosis (ALS) and other illnesses, according to a company press release.

The product will be used to advance first-in-class therapy focused on protecting nerve cells against glutamate toxicity, a process known to contribute to various neurodegenerative disorders, including ALS and Huntington’s disease.

The company was built on the pioneering research of Hilmar Bading, MD, and Jing Yan, PhD, published in 2020. Bading is the co-founder of FundaMental and director of the Department of Neurobiology and the Interdisciplinary Center for Neuroscience in Heidelberg, while Yan is the start-up’s senior director of research.

The duo, along with colleagues from the University of Heidelberg, discovered a whole new class of molecules in their research. These molecules can safely counteract the toxicity of excessive amounts of glutamate – a neurotransmitter or chemical messenger that nerve cells use to communicate with each other – while retaining the protective function of the neurotransmitter.

“I am confident that the successful development of FundaMental’s small molecule inhibitors will mark a milestone in neuropharmacology and perhaps beyond,” said Thomas Schulze, PhD, CEO and co-founder of FundaMental.

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“Having found visionary investors whose goals are aligned with the founder’s goals of stopping neurodegeneration, this vision can now become a reality after many years of dedication and perseverance,” Schulze said.

While glutamate is necessary for normal nerve cell function, higher concentrations of this neurotransmitter can lead to both overstimulation of its receptors and nerve damage. This process is defined as excitotoxicity, a common cause of neurodegeneration.

There have been several attempts to block the receptors implicated in glutamate toxicity. However, almost all did not show benefits because essential glutamate functions were also inhibited.

According to the researchers, the binding of glutamate to its receptors in nerve cells determines the toxic or beneficial role of this neurotransmitter in the brain. When this binding occurs in synapses – the structures that allow nerve cells to send chemical signals to other nerve cells – glutamate has a protective function.

But when glutamate binds its receptors outside synapses, it can trigger nerve cell overactivation and death.

Bading and Yan found that glutamate receptors outside synapses acquired toxic characteristics due to their binding to another protein called TRPM4. By closely examining this relationship using computational methods, they identified small molecules that inhibited the interaction between the two proteins, which prevented the toxic effects of glutamate while maintaining its normal protective effect on nerve cells.

These small inhibitors have been found to decrease nerve cell loss in mouse models of stroke and degeneration of the retina, the innermost, light-sensitive tissue layer of the eye.

Currently, FundaMental is focused on ALS and Huntington’s disease, but the company believes these inhibitors could benefit a wide range of neurodegenerative diseases, such as dementia, stroke, traumatic brain injury and brain disease. Alzheimers.

“It’s probably no exaggeration to call the discovery of the new therapeutic principle of ‘inhibition of an extra-synaptic glutamate-activated death signaling complex’ a breakthrough in neuroscience,” Bading said.

“These inhibitors have the potential to revolutionize therapies for currently incurable neurodegenerative diseases and offer hope to many affected and suffering patients,” he added.

This seed funding round was led by BioGeneration Ventures and Thuja Capital, with participation from other investors including Coparion and High-Tech Gründerfonds.

“We are thrilled to invest and support the FundaMental team as they strive to get these molecules ready for the clinic,” said Keno Gutierrez, PhD, partner at BioGeneration Ventures and incoming Chairman of the Board of Directors of FundaMental.

Michel Briejer, PhD, Board Member and Managing Partner of Thuja Capital added: “We are delighted to be part of this company whose mission is to impact the lives of patients suffering from these neurodegenerative diseases.

“Prof. Bading and Dr. Yan have made a promising and important discovery, opening up the possibility of inhibiting the neurotoxicity of glutamate while leaving its physiologically important aspects unaffected,” Briejer said.

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