crisdesalazine (AAD 2004) / GNT Pharma - LARVOL DELTA

Development of new target protein catalyst compounds as a novel class of hydrogen peroxide scavenger for treatment of Alzheimer's Disease (ACS-Fall 2023) - "We recently investigated the mechanism of action of the drug AAD-2004, which is effective in scavenging H2O2 in neurodegenerative disease mouse model...Lead optimization and in vivo studies for pre-clinical candidate are ongoing. This research supports the possibility of targeting oxidative pathways in AD can have genuine therapeutic efficacy."

Alzheimer's Disease • CNS Disorders • Dementia

Lou Gehrig’s drug by GNT Pharma gets orphan drug designation in Korea, Europe (Korea Biomedical Review) - “GNT Pharma said on Monday that Crisdesalazine (ingredient: aspirin, sulfasalazine), an investigational treatment for amyotrophic lateral sclerosis (ALS) obtained orphan drug designation (ODD) from the Korean and European regulators. The double designation follows its winning ODD from the FDA last year to treat ALS, also known as Lou Gehrig's disease. Along with clinical trial design advice, reduction of screening costs, tax credits, priority screening, and exclusive sales rights, GNT Pharma will also receive support for the drug development of Crisdesalazine from the EMA and Korea’s Ministry of Food and Drug Safety.”

European regulatory • Non-US regulatory • Amyotrophic Lateral Sclerosis • CNS Disorders

REACTIVE ASTROCYTES AS THE CAUSE OF ALZHEIMER'S DISEASE (ADPD 2023) - "From these mechanistic insights we have identified MAOB and H2O2 as molecular targets and developed highly potent and selective drug candidates, KDS2010(Seremabi) and AAD2004(Crisde salazine), which are now in phase I clinical trials. We have delineated the detailed molecular and cellular mechanisms of how reactive astrocytes contribute to neurodegenerative diseases. The novel concepts and tools that we have developed hav e been extremely valuable in developing novel therapeutic approaches to diagnose and cure the various neurodegenerative diseases such as Alzheimer's disease."

Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation

GNT Pharma enters Phase 1 clinical trial for a new drug candidate for dementia [Google translation] (CEO Score Daily) - "GNT Pharma...has begun full-scale additional research into phase 1 clinical trials of new drug candidates for the treatment of dementia. According to related industries on the 10th, GNT Pharma recently started recruiting patients for phase 1 clinical trial of AAD-2004 (ingredient name: Crisdesalazine), a new drug candidate for dementia....In this phase 1 clinical trial on humans, after oral administration of AAD-2004 to healthy adults between the ages of 19 and 45, safety and tolerability will be evaluated. A higher dose (400 mg or 600 mg) will be administered as a single escalating dose, or a smaller dose (100 mg or 200 mg) will be administered multiple times (two times a day, total of 15) escalating doses compared to the previous phase 1 clinical trial....GNT Pharma plans to start phase 2 clinical trials next year."

Enrollment open • New P2 trial • CNS Disorders

Inhibition of monoamine oxidase B prevents reactive astrogliosis and scar formation in stab wound injury model. (PubMed, Glia) - "Notably, we identified two potent pharmacological tools to attenuate scar-forming astrogliosis-the recently developed reversible MAO-B inhibitor, KDS2010, and an H O scavenger, crisdesalazine (AAD-2004). Our results implicate that inhibiting MAO-B activity has dual beneficial effects in preventing astrogliosis and scar-formation under brain injury, and that the MAO-B/H O pathway can be a useful therapeutic target with a high clinical potential."

Journal • CNS Disorders • Vascular Neurology • GFAP

Korea discovers key indicators for Alzheimer’s disease (Biospectrumasia) - "Korean researchers at the Center for Cognition and Sociality, within the Institute for Basic Science (IBS) and Korea Institute of Science and Technology (KIST) announces the discovery of key indicators for neurodegeneration in Alzheimer’s disease....The research team has demonstrated that the severity of ‘reactive astrocytes’ is a key indicator for the onset of AD, raising profound implications of the current theory of AD mechanism....The research team verified that all of these events of the AD pathology were halted by a recently developed reversible MAO-B inhibitor, KDS2010 or a potent H2O2 scavenger, AAD-2004. This reinforces that severe reactive astrocytes are the cause of neurodegeneration..."

Preclinical • Alzheimer's Disease • CNS Disorders

Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer's disease via HO production. (PubMed, Nat Neurosci) - "Mechanistically, excessive hydrogen peroxide (HO) originated from monoamine oxidase B in severe reactive astrocytes causes glial activation, tauopathy, neuronal death, brain atrophy, cognitive impairment and eventual death, which are significantly prevented by AAD-2004, a potent HO scavenger. These HO-induced pathological features of AD in GiDs are consistently recapitulated in a three-dimensional culture AD model, virus-infected APP/PS1 mice and the brains of patients with AD. Our study identifies HO from severe but not mild reactive astrocytes as a key determinant of neurodegeneration in AD."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

SEVERE REACTIVE ASTROCYTES PRECIPITATE PATHOLOGICAL HALLMARKS OF ALZHEIMER’S DISEASE VIA EXCESSIVE H2O2-PRODUCTION (ADPD 2019) - "...These were significantly prevented by AAD-2004, a potent H2O2 scavenger. These neurodegenerative markers were consistently observed in 3D culture AD model, virus-infected APP/PS1 mice and human AD brain. Our study identifies the severe reactive astrocytes, but not mild reactive astrocytes, as a key determinant of neurodegeneration in AD."