Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: Galantos Pharma, Neurodyn
GLN-1062 is an inactive prodrug of galantamine. GLN-1062 was synthethized to be more lipohilic than galantamine in order to facilitate its entry into the brain and its ability to enzymatically cleave there to release the active drug. The compound was developed at Galantos Pharma with the goal of increasing the brain bioavailability and reducing the peripheral side effects of galantamine. Additional goals are to increase the effective dose in the brain and provide a therapeutic effect rapidly, without the gradual titration up to effective dose that is commonly necessary with oral acetylcholinesterase inhibitors. This drug is delivered as a nasal spray formulation to shift exposure away from the gastrointestintal system. In 2013 GLN-1062 was sold to the Canadian company Neurodyn for clinical development.
Preclinically, GLN-1062 was reported to improve cognition more strongly than did comparable doses of galantamine in mice, and to reduce vomiting in ferrets. Another study claimed five times higher potency than galantamine in rescuing scopolamine-induced memory impairment in mice, as well as improved memory performance and reduced plaque load in 5xFAD transgenic mice. Pharmacologically, GLN-1062/Memogain was reported to achieve 10 times higher concentration in the brain than blood (see Maelicke et al, 2010; Maelicke 2011, Alzheimers & Dementia).
In September 2014, Neurodyn issued a press release claiming that an initial trial in healthy young and old volunteers showed positive results. According to the company, the study primarily compared safety, tolerability, and pharmcokinetics of Memogain to the daily recommended dose of galantamine (16 mg) and donepezil (10 mg). All tested doses of Memogain were reportedly safe and well-tolerated; participants reported nausea at 16 mg of galantamine but not until 44 mg of Memogain. The company further claims that Memogain heightened vigilence and short-term memory in both young and old volunteers compared with untreated controls (see press release).
As of October 2014, no trials were listed in clinicaltrials.gov or the WHO trials register.
- Maelicke A, Hoeffle-Maas A, Ludwig J, Maus A, Samochocki M, Jordis U, Koepke AK. Memogain is a galantamine pro-drug having dramatically reduced adverse effects and enhanced efficacy. J Mol Neurosci. 2010 Jan;40(1-2):135-7. PubMed.
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