Next, the ADAM protease inhibitors can be used to prevent the sequential alpha cleavage that occurs in the Notch extracellular domain and renders it 'recognisable' for the gamma secretase
His findings show that, when damaged or excessively activated in human cells, Ras, through gamma secretase
, activates a protein known as Notch-1, which in turn triggers a chain of events that allow cancer cells to grow.
EnVivo Pharmaceuticals, a company dedicated to developing a broad range of novel central nervous system (CNS) therapies, today announced the initiation of a Phase 2 clinical trial of EVP-0962, its potent and selective gamma secretase
modulator (GSM), in healthy volunteers and in volunteers with mild cognitive impairment or early Alzheimer's disease.
By working too much, it sends the wrong message to the Beta secretase
, which in turn starts to produce more amyloid Beta.
Greengard found that before gamma secretase
can even get started, the protein he discovered, which he calls gamma secretase
activating protein, must tell the enzyme to make beta amyloid.
By blocking gamma secretase
, there is less amyloid beta formed and potentially
Targeting this axis may have therapeutic potential and gamma secretase
inhibitors such as GSI should be considered for early-phase trials.
In previous studies, the Temple researchers discovered that 5-lipoxygenase, an enzyme long known to exist in the brain, controls the activation state of gamma secretase
, another enzyme that is necessary and responsible for the final production of amyloid beta.
Lilly's drug was designed to reduce the body's production of the plaques by inhibiting the activity of an enzyme, called gamma secretase
, that is believed to play an important role in formation of the plaque.
INDIANAPOLIS, August 17, 2010 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) will halt development of semagacestat, a gamma secretase
inhibitor being studied as a potential treatment for Alzheimer's disease, because preliminary results from two ongoing long-term Phase III studies showed it did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.
investigational gamma secretase
inhibitor for the treatment of mild to moderate
pulled the plug last month on its phase III study of semagacestat, a gamma secretase
inhibitor designed to reduce the aggregation of beta-amyloid into brain plaques.