Alzheimer's Disease
Alzheimer's disease is a progressive and debilitating neurodegenerative disorder and is the most common form of dementia. In 2010 it was estimated that there were 35 million people suffering from dementia globally. Symptoms of Alzheimer’s disease include memory loss, change in mood and personality, and a decline in cognitive abilities.
Existing Alzheimer’s disease treatments only provide symptomatic relief and there remains a high need for the development of new, disease modifying medicines that affect the progression of the disease. The global disease treatment market for Alzheimer’s disease is currently estimated to be worth $8.3 billion, a figure that is expected to rise with the development of disease modifying drugs.
The precise cause of Alzheimer’s disease is not known but it is generally thought to be due to multiple factors rather than a single cause. The greatest risk factor for Alzheimer’s is advancing age with most patients being age 65 or over.
Tangles and the role of tau
One of the characteristics of Alzheimer’s disease is the formation in the brain of ‘tangles’ of abnormal protein. A protein called tau plays an important role in stabilising microtubules, a structural component of brain cells that transport nutrients and vital molecules to different parts of the nerve. The brains of Alzheimer’s patients contain abnormal tau protein that destabilises the microtubule structure to cause the malfunction of the brain cells transport and communication system and later cause cell death, and ultimately disease symptoms. The abnormal protein tau combines together to form large aggregates inside the brain cells called neurofibrillary tangles. The abnormal tau protein is converted from normal tau via a process called hyperphosphorylation.
Alzheimer’s disease is one of a number of neurodegenerative diseases where tau protein tangles are found in the brain, and collectively these diseases are known as ‘tauopathies’.
OGA: A potential disease modifying approach
Summit is using its Seglin™ technology platform to target O-linked N-acetylglucosaminidase (‘OGA’), an enzyme that represents a potential disease modifying approach for the treatment of Alzheimer’s disease and other neurological disorders. OGA has emerged as a target in the search for new drugs as its inhibition reduces levels of abnormal or hyperphosphorylated tau protein in the brain meaning it has the potential to protect brain cells and prevent the formation of the neurofibrillary protein tangles.
Summit has developed novel Seglin compounds that are potent and very selective inhibitors of the OGA enzyme. Initial proof of concept has been established in human cell models with the Seglins being shown to reduce the levels of hyperphosphorylated tau protein.
