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Re: millman post# 7073

Thursday, 02/28/2013 1:18:17 PM

Thursday, February 28, 2013 1:18:17 PM

Post# of 20775
Thanks for sharing...

"While bapineuzumab failed to show clinical benefit, the use of biomarkers clearly demonstrated the drug had engaged the target, reduced the amount of plaque and slowed neurodegeneration based upon the decrease in the amount of tau protein measured in the cerebral spinal fluid (CSF)."

"However, we are currently focused on optimizing CONJUMAB-A using our own antibody IN-N01 which targets the N-terminus of Aß. We believe IN-N01 to be superior to bapineuzumab because of its reduced potential to cause inflammation which results from our reengineering of the originally produced IG1 class antibody into an IgG4 class antibody. We believe this safety feature is particularly important for antibodies that bind Aß aggregates and not just soluble single monomeric Aß. Among several potential indications, we have decided to focus on age related macular degeneration (AMD) for proof of concept studies since AMD and AD share several similarities while the eye offers less challenge for delivering the drug. "


"An important step in establishing proof-of-principle was the initial data generated through our collaboration with iNovacia to evaluate compounds synthesized by Lonza for Intellect. The data demonstrated the conjugation of the antioxidant molecule to an amino acid does not reduce its antioxidant activity. Pending adequate financial resources, these studies, which are almost complete, will allow us to select a drug candidate to take into development, providing the trigger for us to move forward with LONZA into an expanded manufacturing project, bringing us closer to the submission of an Investigational New Drug application."



Melatonin and Alzheimer's Disease
Improving Sleeplessness and Sundowning With Melatonin

From John Casey
Updated August 05, 2008

LifeWire) - Alzheimer's disease is a devastating illness, but unique treatments like the hormone melatonin may be able to improve difficult symptoms such as sleeplessness and sundowning.

Sundowning refers to behavioral disturbances that are fairly common in Alzheimer's disease and tend to occur in the early evening. For reasons that aren't entirely clear, many people with Alzheimer's exhibit increased confusion, anxiety, agitation and even aggression at the end of the day. Luckily, there's evidence that melatonin can help with sundowning and related sleep disturbances.

Alzheimer's and "Sundowning"

According to the Alzheimer's Association, nearly a fifth of individuals with Alzheimer's will experience periods of sundowning, usually in the middle stages of the disease. Sundowning takes a toll on those who have Alzheimer's and contributes greatly to caregiver stress and fatigue. It reportedly plays a major role in decisions to move those with Alzheimer's from home care to nursing homes.

Melatonin has many roles in the body, but it is particularly important in sleep regulation. Melatonin is produced in the brain, specifically by the pineal gland. This gland releases its peak level of melatonin at dusk, and the hormone appears to be instrumental in the cascade of changes that we call falling asleep.

Alzheimer's and Melatonin

Research has long established that melatonin levels naturally decrease with age, but people with Alzheimer's disease have especially low levels -- sometimes only half as much as people of the same age who don't have the disease. Also, sleep disturbances are frequently a symptom of Alzheimer's. In recent years, a number of studies have reported benefits of supplemental melatonin, not only for reducing Alzheimer's-related sleep problems, but for sundowning as well.

Melatonin may also have further benefits. It's a powerful antioxidant, acting to counter harmful chemical reactions that can damage cells. It appears to have specific neuroprotective qualities, meaning that it helps protect nerve and brain cells from damage. There's also evidence that having an insufficiency of melatonin plays a role in depression.

Some studies suggest that the hormone can improve mild cognitive impairment, although researchers emphasize that the effect is limited and that melatonin isn't a "cure" for full-blown Alzheimer's disease. Some researchers caution that the impact of the hormone would be relatively less in late-stage Alzheimer's.

On the positive side, melatonin has few if any side effects, in large part because it's processed and removed from the body very quickly. However, that quality and the multiplicity of its effects make melatonin less than ideal as a medication.

Researchers have begun developing "melatoninergic" or melatonin-type drugs that are longer-acting and have more specific targets. Rozerem (ramelteon) has won FDA approval for long-term treatment of sleep disturbances. Another drug, Valdoxan (agomelatine), is meant to treat major depressive disorders and is also undergoing clinical trials for FDA approval.

Thus far, no melatonin-type medications have been developed specifically for Alzheimer's disease or sundowning.

What You Can Do

Since melatonin is classified as a supplement, it's available without a prescription. But before you give the hormone to someone with Alzheimer's, you should consult his or her physician, who'll be able to determine whether it makes sense and fits the person's symptoms. Studies of melatonin for treating Alzheimer's have reported benefits from doses of 3 to 9 mg of melatonin per day.

http://alzheimers.about.com/lw/Health-Medicine/Alternative-treatments/Melatonin-and-Alzheimers-Disease.htm

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