Separate teams of investigators have reported new insights into how the brain disposes of metabolic waste via the glia-based lymphatic system, or glymph system. In two papers published in Nature on Feb. 28, 2024, scientists from Washington University in St. Louis described how in sleeping animals, the synchronized activity of neurons drove ionic gradients that facilitated the movement of fluid through brain tissue. And researchers from the Massachusetts Institute of Technology showed that, in a mouse model of Alzheimer’s disease (AD), the glymphatic system mediated clearance of amyloid-β after sensory stimulation at a 40-Hertz rhythm.
In the end, Minerva Neurosciences Inc. NDA submission wasn’t able to overcome the U.S. FDA’s concerns regarding data for dual 5-HT2A/sigma 2 antagonist roluperidone. The agency issued a complete response letter (CRL) for the application, which had been seeking approval as the first treatment specifically targeting negative symptoms of schizophrenia.
Korean neurodegenerative disease-focused Aribio Co. Ltd. gained the U.K.’s regulatory clearance to start the phase III Polaris-AD trial on AR-1001 (mirodenafil), an investigative therapy for early Alzheimer’s disease (AD). The U.K.’s Medicines and Healthcare products Regulatory Agency gave notice of acceptance to Seoul, South Korea- and San Diego-based Aribio for the clinical study on Feb. 21 after “confirming a favorable ethical opinion,” Aribio said. AR-1001 is an oral phosphodiesterase-5 inhibitor under development to treat early AD.
With the number of people with dementia in Australia expected to nearly double by 2054, the federal government is funding a new AU$50 million (US$32.76 million) biomedical and med-tech incubator program to develop new therapies, medical devices and digital health technologies to address dementia and cognitive decline.
The biological processes giving rise to the central nervous system symptoms of long COVID remain a mystery. But multiple studies suggest they do not appear to be a result of a direct viral infection of brain tissue. The latest such research, which appeared online in Nature Neuroscience on Feb. 16, 2024, demonstrated that local immune response in brain tissues persisted long after SARS-CoV-2 virus had disappeared.
Based on positive phase III study data, Applied Therapeutics Inc. plans to take its CNS-penetrant aldose reductase inhibitor to the U.S. FDA to talk about an NDA for treating the rare disease sorbitol dehydrogenase (SORD) deficiency. Interim data from 12 months of treatment showed govorestat (AT-007) hit the study’s primary endpoints along with several key secondary endpoints. The double-blind, placebo-controlled registrational study of patients ages 16 to 55 is ongoing, with another 12 months of data yet to come. SORD, a hereditary axonal neuropathy created by sorbitol dehydrogenase gene mutations, affects about 3,300 people in the U.S. and about 4,000 in Europe, according to Applied Therapeutics.
When founders of Latigo Biotherapeutics Inc. first set out a few years ago to establish a biopharma firm focused in the area of pain, the plan had been to get a head start by in-licensing promising assets in the space. But that proved easier said than done. “With the exception of very early chemical matter” from the Lieber Institute for Brain Development, “we really couldn’t find anything else of quality to bring in, which I think is a testament to how little pain research and investment was ongoing in pharma and academia,” said Sean Harper, co-founding managing director at Westlake Village Biopartners, which founded Latigo in 2020 and led the firm’s $135 million series A round.
South Korean biopharmaceutical firm GNT Pharma Co. Ltd. on Feb. 13 reported positive findings from a domestic phase III trial of its neuroprotectant therapy, nelonemdaz (NEU-2000), for patients with acute ischemic stroke.
Otsuka Pharmaceutical Co. Ltd.’s AVP-786 missed the primary endpoint for a third time in a phase III trial for agitation associated with dementia due to Alzheimer’s disease (AD). Two previous phase III trials also failed to show statistical significance for AVP-786.
The European Commission approved two therapies for progressive, genetic diseases: Biogen Inc.’s Friedreich’s ataxia drug, Skyclarys (omaveloxolone), and Crispr Therapeutics AG’s CRISPR/Cas9 gene therapy for sickle cell disease and transfusion-dependent beta-thalassemia, Casgevy (exagamglogene autotemcel, exa-cel).