Alzheimers - are we any nearer?

    
     Alzheimer's Disease, medically speaking  is the sort of medical dilemma that AIDS was a few short years ago. Incurable, untreatable, with any effective treatment seeming a long way off in the future.
    So what is it?  Well, it used to go by a lot of names.  Senile dementia, presenile dementia, losing one's mind, old age and various other inaccurate names.
     A progressive, neurodegenerative disease characterized by loss of function and death of nerve cells in several areas of the brain, leading to loss of cognitive function such as memory and language. The cause of nerve cell death is unknown but the cells are recognized by the appearance of unusual  protein filaments in the nerve cells.  Plaques form when protein pieces called beta-amyloid clump together. Beta-amyloid comes from a larger protein found in the fatty membrane surrounding nerve cells.  Beta-amyloid is chemically "sticky" and gradually builds up into plaques.
   The most damaging form of beta-amyloid may be groups of a few pieces rather than the plaques themselves. The small clumps may block cell-to-cell signaling at synapses. They may also activate immune system cells that trigger inflammation and devour disabled cells.
       The oldest category of medications are known as cholinesterase inhibitors  some of which are named below.

•  Aricept^®
•  Exelon™
•  Reminyl^®

Cholinesterase inhibitors help by improving the ability of impaired nerve endings to transmit messages from one nerve cell to another.  The drugs are only temporarily effective, if they are effective at all and the benefits gradually wear off.
    The good news is that there are some promising new drugs currently being researched but not yet ready for general use. 
    Three drugs being highlighted at the Alzheimer's Association International Conference are called solanezumab, aducanumab and gantenerumab. (The "mab" at the end of the drug name stands for monoclonal antibody). They are antibodies that specifically attack amyloid thought to be the cause of much  of the damage.
     Aducanumab, also known as BIIB037 and made by Biogen, appears to be clearing the amyloid from the brains of patients, researchers told the meeting. There's also some evidence that this might be improving test scores in the patients who got the very highest doses.  Biogen is moving ahead to a phase III study - the very last stage before seeking Food and Drug Administration approval. 
      The second drug group presented at the meeting is a BACE inhibitor that's being developed by Merck, . Researchers don't know exactly how it does what it does. They don't yet know whether it will help patients.  BACE inhibitors block an enzyme that fragments a large protein in the brain into smaller pieces of sticky beta amyloid, a substance that forms telltale plaques in the brains of Alzheimer's patients. Blocking the enzyme blocks production of beta amyloid.  This drug has been under development for ten or more years.
     In a study, which was mainly designed to check the safety of the drug, researchers assigned 30 patients to take one of three drug dosages or a placebo for seven days. Patients on the highest doses of the drug saw reductions in beta amyloid in their spinal fluid of over 80 percent. Researchers say they saw no evidence of adverse effects.   "We can reduce amyloid to unprecedented levels," said Dr. Mark Forman, a senior principal scientist at Merck, the company that's developing the drug.
   The problem, skeptics say, is that medications have been used to reduce beta amyloid before, and those had no clinically meaningful benefits for patients, at least for those already diagnosed with the disease. There have been some signs that lowering beta amyloid may be helpful for people who haven't yet begun to show symptoms of memory loss.  Forman said he thinks BACE inhibitors have a better chance of working, however.
    "BACE inhibitors blocks the generation of amyloid at the very first step in its production. It's very different from what some of the other studies have done with antibodies that are really promoting the clearance of beta amyloid after it's formed," he said.  Experts agreed that the drug seems to work well to lower beta amyloid, but, "It remains to be seen when you can do that whether  it will produce a useful, lasting clinical benefit,"

The third category of medication  are known as Biologic Response Modifiers.
       ENBREL  was the first biologic approved for  severe rheumatoid arthritis. is grouped within a class of medications called biologic response modifiers, or biologics. By working on the immune system, biologics block proteins that contribute to the disease process.  Tumor necrosis factor (TNF) is a substance made by the body's immune system. People with inflammatory diseases such as rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, juvenile idiopathic arthritis, and ankylosing spondylitis have too much TNF in their bodies. ENBREL reduces levels of the active form of TNF.. It exercises an anti-inflammatory effect.  Because ENBREL suppresses the immune system, patients are at a greater risk for getting serious infections..
     This is exciting stuff and although we don't yet know where it is going to lead, it is hopeful  that a combination of some of these drugs will have as beneficial an effect on Alzheimers Disease as the drug cocktail used for treating aids have had on that disease.