Alzheimer's disease(Mitorx Therapeutics)

Asceneuron, a Switzerland-based biotechnology company, has raised another $100 million to support its work developing drugs that target a protein linked to Alzheimers disease and other nerve-destroying disorders.Disclosed Tuesday, the Series C fundraising round received more interest than Asceneuron initially expected. The holding company behind Novo Nordisk led the round. Healthcare investors EQT Life Sciences, OrbiMed, SR One, Sofinnova Partners and GSK Equity Investments also participated, as did the venture arms of Johnson & Johnson and Merck KGaA.Asceneuron plans to use the money to push its most advanced experimental drug into mid-stage testing as a possible treatment for Alzheimers. Taken as a capsule, the drug is designed to block OGA, an enzyme that removes a specific chemical from proteins. Research indicates this chemical helps prevent toxic proteins from bunching together, which is a key characteristic of diseases like Alzheimers and Parkinsons.Specifically, Asceneurons drug is meant to keep tau proteins from aggregating. Aside from another protein called amyloid beta, tau has received the most attention from drugmakers as a target for Alzheimers therapies.The few Alzheimer's medicines approved by the Food and Drug Administration, including Eli Lillys just-cleared Kisunla, act on amyloid beta and are delivered as intravenous infusions. Yet, Asceneuron contends that the way its drug works and the way its taken make it an ideal therapy for patients with the memory-robbing disease.The companys CEO, Barbara Angehrn Pavik, said in a statement that the latest funding round further validates the potential of Asceneurons research.Alzheimers disease is undergoing a transformational moment. Millions are afflicted by this devastating disease and there are very few therapeutic options, said Naveed Siddiqi, a senior partner in the venture investments division of Novo Holdings. Validated biomarkers are allowing for more focused and rapid development.Asceneuron was founded in 2012 as a spinout from Merck KGaA. The biotech started with just 6 million Swiss francs, or about $6.4 million, in seed funding. By 2015, it had raised another 30 million Swiss francs through a Series A round in which Sofinnova Partners, SR One, Kurma Partners and Johnson & Johnson Innovation contributed.In the years since, startups taking aim at neurodegeneration have continued to attract investments. Cerevance, a biotech focused on neurological and psychiatric disorders, launched in 2016 with $36 million and backing from Takeda Pharmaceutical. In the spring of 2022, Merck & Co. spent $25 million and offered up to $1.1 billion on the back end to take over a Cerevance program targeting Alzheimers.More recently, Therini Bio raked in $36 million to support the development of an Alzheimer's drug intended to stop the inflammation and neuronal damage caused by a protein known as fibrin. The money came from an investor group that included Eli Lilly and the venture arms of Merck and Sanofi.MapLight Therapeutics, meanwhile, in October completed a $225 million Series C round. Novo Holdings led the round, and was joined by MapLights existing investors as well as new ones like 5AM Ventures and Cowen Healthcare Investments. The biotech said it will use the money to advance an experimental medicine for schizophrenia and Alzheimers disease psychosis into mid-stage testing. '

Researchers combined artificial intelligence and chemical biosensors to ferment the precursor of an Alzheimer's drug in bacteria. Galantamine is a common medication used by people with Alzheimer's disease and other forms of dementia around the world to treat their symptoms. Unfortunately, synthesizing the active compounds in a lab at the scale needed isn't commercially viable. The active ingredient is extracted from daffodils through a time-consuming process, and unpredictable factors, such as weather and crop yields, can affect supply and price of the drug. Now, researchers at The University of Texas at Austin have developed tools -- including an artificial intelligence system and glowing biosensors -- to harness microbes one day to do all the work instead. In a paper in Nature Communications, researchers outline a process using genetically modified bacteria to create a chemical precursor of galantamine as a byproduct of the microbe's normal cellular metabolism. Essentially, the bacteria are programmed to convert food into medicinal compounds. "The goal is to eventually ferment medicines like this in large quantities," said Andrew Ellington, a professor of molecular biosciences and author of the study. "This method creates a reliable supply that is much less expensive to produce. It doesn't have a growing season, and it can't be impacted by drought or floods." Danny Diaz, a postdoctoral fellow with the Deep Proteins research group in UT's Institute for Foundations of Machine Learning (IFML), developed an AI system called MutComputeX that is key to the process. It identifies how to mutate proteins inside the bacteria to improve their efficiency and operating temperature in order to maximize production of a needed medicinal chemical. "This system helped identify mutations that would make the bacteria more efficient at producing the target molecule," Diaz said. "In some cases, it was up to three times as efficient as the natural system found in daffodils." The process of harnessing microbes to produce useful byproducts is nothing new. Brewers use yeast to make alcohol, and bacteria help create cheese and yogurt. Microbial fermentation is currently used to make certain types of insulin for diabetes treatment, hormones and recombinant proteins used in several drugs such as autoimmune treatments, and even vaccines. But applying AI in the process is relatively new and expands what is possible with microbial fermentation. The research team genetically modified E. coli to produce 4-O'Methyl-norbelladine, a chemical building block of galantamine. The complex molecule is in a family of compounds extracted from daffodils that have medicinal uses in treating conditions such as cancer, fungal infections and viral infections, but using microbial fermentation to create a chemical in this family is new. The scientists also created a fluorescent biosensor to quickly detect and analyze which bacteria were producing the desired chemicals and how much. When the biosensor, a specially created protein, comes into contact with the chemical researchers wanted to create, it glows green. "The biosensor allows us to test and analyze samples in seconds when it used to take something like five minutes each," said Simon d'Oelsnitz, a postdoctoral researcher formerly at UT Austin and now at Harvard University, the first author of the paper. "And the machine learning program allows us to easily narrow candidates from tens of thousands to tens. Put together, these are really powerful tools." Wantae Kim, Daniel Acosta, Tyler Dangerfield, Mason Schechter, James Howard, Hannah Do, James Loy, Hal Alper and Y. Jessie Zhang of UT and Matthew Minus of Prairie View A&M University were also authors of the paper. The research was supported by the National Institute of Standards and Technology, the Air Force Office of Scientific Research and the National Institutes of Health, and the National Science Foundation supports IFML. Computing resources were provided by Advanced Micro Devices. Those involved in this research have submitted required financial disclosure forms with the University, and Ellington, Diaz and d'Oelsnitz have filed a patent application on materials described in this text. Diaz and d'Oelsnitz are each involved with startups related to this research.