CurXceL Research & Development
1. Primary Therapeutic Target
Our primary therapeutic target will be Alzheimer's Disease(AD). AD is the most common cause of progressive cognitive dysfunction. AD affects approximately four million Americans and is estimated that by the year 2050, fourteen million Americans are expected to be afflicted by the disease. By age 85, a person will have a 47% probability of being afflicted by AD. Currently, over 100,000 deaths each year in the United States are attributed to AD with a total annual cost for treatment of AD rapidly approaching $100 billion.
2. Summary of the Status of Current Research and Treatment
AD research is one of the most active areas of investigation in the field of neuroscience; the disease is being investigated at every level.
- Basic scientists are trying to unravel how AD causes brain cells to die.
- Epidemiologists are searching for environmental and nutritional factors that may contribute to the risk of developing the disease.
- Molecular geneticists are looking for new gene mutations that can cause the disease.
- Clinical geneticists are trying to identify genetic susceptibility factors.
- Clinicians and pharmacologists are looking for treatments that can delay the onset, slow the progression, improve the symptoms, and perhaps eventually cure the disease.
As a result of the complexity of the disease, current treatment only slows the progression of AD when caught in its early stages. For patients with advanced AD, present drug treatments only alleviate the cognitive impairment but does not reverse the debilitating effects of the disease.
Although genetic association of the onset of AD has recently received a great deal of mass-media attention, gene-associated AD constitutes less than 7% of all reported AD cases and the true cause of AD is still unknown. Over 90% of the AD cases are without any known cause, which is called Sporadic AD, suggesting that other mechanisms are involved in the pathogenesis of AD. The single most common denominator in the onset of AD is the accumulation of beta-amyloid(bA) in the brain in the form of senile plaque.
To date, there is no drug that counteracts completely the degenerative process in AD. Acetylcholinesterase inhibitors relieve only some symptoms of AD, but do not affect the underlying course of the disease.
There is no cure yet on the horizon for Alzheimer's Disease.
However, next generation of pharmacological approaches may prove to be more effective than the existing drugs in the market. Current pharmacological approaches related to AD preventive and neuroprotective interventions include antioxidant therapy, acetylcholinesterase inhibitors, calcium channel blockers, sulfonated compounds, triaminopyridine nonopiate analgesic drug, non-steroidal anti-inflammatory drugs, COX-2 inhibitors and low molecular lipophilic compounds that can activate neurotrophic factor signaling pathways. Of the many pharmacological approaches that are currently being pursued, two of the more favored pharmacological methods are beta-amyloid inhibitors and neurotrophic enhancers.
3. Why beta-amyloid
Research has shown that AD patients' brains contain a large volume of sticky amyloid plaques. Although it is not known if the plaques are a cause or a result of AD, studies show they lead to death of brain cells. The plaques' main ingredient is bA, a fragment of a normal body protein that goes awry in people with AD. bA is generated from APP (amyloid protein precursor protein) through cleaving action of enzyme called beta and gamma secretase. Some patients produce too much bA and others simply do not properly clear it out of the brain. At a certain concentration, bA has been found to be toxic to brain cells. While it is not yet known whether plaque buildup causes AD or is an early byproduct of AD, the bA Theory has been widely accepted.