New treatment candidate given green-light to treat dementia and alzheimer’s disease

Researchers have recently discovered a new treatment candidate that halts neurodegenerative symptoms in mouse models with dementia and Alzheimer’s disease. The treatment candidate has also been shown to reverse the adverse effects of these disorders. The results of the study were published on June 8 in the International Journal of Molecular Sciences by a research team based at the Tohoku University. Additionally, the treatment candidate has been given the go-ahead by Japan’s governing board, and  human clinical trials are set to commence in 2022. According to paper author of the study, professor Kohji Fukunaga—who is based at the Tohoku University’s Graduate School of Pharmaceutical Sciences—they discovered that the treatment candidate known as SAK3 rescued neurons in a majority of protein-misfolding neurodegenerative diseases. These include diseases such as frontotemporal dementia, Huntington disease, Lewy body dementia, and Alzheimer’s disease. In an initial study, the researchers had determined that the SAK3 molecule improved learning and memory in mouse models that had Alzheimer’s disease. Moreover, past studies have shown that SAK3 enhances the functioning of the cell membrane channel by boosting neuronal activity in the brain. Generally, SAK3 boosts neurotransmitter releases of dopamine and acetylcholine which greatly reduce Alzheimer’s disease and Lewy body dementia. Ca2+, the base structure of SAK3, is believed to trigger a change from resting to active in neuronal activity. Once the Ca2+ is dysregulated in the brain, it reduces the dopamine and acetylcholine releases. This results in a dysregulated system that causes uncoordinated motor function as well as cognitive confusion. Additionally, SAK3 binds to the subunit of the channel, causing the enhancement of neurotransmission and improving cognitive deficits. The researchers also noted that the same process worked on a mouse model of Lewy body dementia, which is marked by a build-up of proteins known as Lewy bodies. And even after the onset of cognitive impairment, SAK3 administration greatly prevented the progression of neurodegenerative features such as reduced cognition and motor dysfunction. Interestingly, Aduhelm—which is the Alzheimer’s drug that was recently approved by the U.S. Food and Drug Administration, was observed to reduce the number of amyloid plaques in the brain. However, it is uncertain whether the amyloid reduction further prevents motor or cognitive decline in patients. In comparison, Fukunaga believes that SAK3 helps eliminate amyloid plaque, especially in mice. Fukunaga goes on to say that SAK3 further helps control the destruction of misfolded alpha-synuclein. Usually, alpha-synuclein regulates neurotransmitter pathways in the brain. This protein can at times misfold and aggregate, causing what researchers believe to be the major cause of neurodegenerative symptoms. This aggregation can further result in the complete loss of the dopamine neuron, which aids with memory and learning. “We found that chronic administration of SAK3 significantly inhibited the accumulation of alpha-synuclein in the mice. “SAK3 is the first compound targeting this regulatory activity in neurodegenerative disorders. SAK3 administration promotes the destruction of misfolded proteins, meaning the therapeutic has the potential to solve the problems of diverse protein misfolding diseases such as Parkinson’s disease, Lewy body dementia, and Huntington disease, in addition to Alzheimer’s disease.” Fukunaga notes.