AgeneBio has received a $750,000 grant from the Alzheimer’s Drug Discovery Foundation (ADDF) to support the development of a novel GABAA discovery program targeting hippocampal overactivity in the brain, which is thought to contribute to neurodegeneration and cognitive decline in Alzheimer’s disease (AD) patients.
AgeneBio’s pipeline of therapies is based on research showing that overactivity in the hippocampus (the part of the brain responsible for emotion, memory, and learning) contributes to cognitive impairment and drives neurodegeneration later on.
This overactivity is characteristic of mild cognitive impairment (MCI) due to AD, the symptomatic pre-dementia stage before AD fully develops.
AgeneBio’s lead candidate, AGB101, is now ready to enter Phase 3 development. If approved, it will be the first therapeutic targeting hippocampal overactivity and potentially the first therapeutic to slow down progression and delay onset of AD’s dementia.
“AgeneBio’s GABA-A discovery program is a novel approach to delaying the onset of Alzheimer’s dementia by targeting the marked hippocampal overactivity that is present during MCI due to AD,” Sharon Rosenzweig-Lipson, PhD, said in a press release. Rosenzweig-Lipson is primary investigator on studies supported by this grant and AgeneBio’s vice president of research and development. “We are very grateful to the ADDF, a leader in supporting Alzheimer’s research, for its long-term support and confidence in our science. We have made significant progress in advancing the chemistry of our GABAA program and look forward to furthering our program with this support.”
GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the mammalian central nervous system. Its main role is to reduce neuronal excitability throughout the nervous system. In humans, GABA also is thought to be responsible for the regulation of muscle tone. GABA limits overactivity of neurons. Compounds that enhance its activity are well-positioned to attenuate and control the consequences of this overactivity in the hippocampus.
Backing AgeneBio’s program is research led by its founder and chief scientific officer Michael Gallagher, PhD, who lectures at Johns Hopkins University. In addition, for the past five years the pharmaceutical company has partnered with Hager Biosciences, a drug discovery organization, to advance the chemistry of the GABA-A discovery program. This program aims to enhance the activity of GABA at the GABAA alpha-5 (a5) receptor, which has been shown in preclinical studies to improve memory function.
With the new funding, Rosenweig-Lipson and a team of Hager researchers will continue their work on this discovery program.
“As the GABAA program continues to progress, we are very optimistic about its potential to address MCI due to AD and delay the onset of Alzheimer’s dementia,” said Jerry McLaughlin, AgeneBio’s president and CEO. “While we are in the early stages of development, we envision the potential for GABAA to positively impact this medical crisis facing millions of patients and their families. We are honored to continue our valued relationship with the ADDF and to be a part of its vital work to find effective Alzheimer’s therapies.”