Saturday, August 09, 2008

TauRx Therapeutics-- New treatment halts progress of Alzheimer's disease

The results of the Phase 2 study of TauRx's new treatment strongly suggest that it is possible to halt progression in mild and moderate Alzheimer's. TauRx is continuing to refine its treatment and hopes that restoration may be possible at least at the earlier stages with improved versions of its drug. Tangles are already destroying nerve cells in parts of the brain critical for memory in people in their fifties and upwards. The ultimate goal is to develop a product that is convenient for patients that could be widely used at the very earliest stages of the disease, long before patients experience the first symptoms of Alzheimer's.
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Wednesday, August 06, 2008

Monday, January 29, 2007

The Seven Stages of Alzheimer's

"Experts have documented common patterns of symptom progression that occur in many individuals with Alzheimer’s disease and developed several methods of “staging” based on these patterns."

Read the article The Alzheimer's Reading Room: The Seven Stages of Alzheimer's

Saturday, November 18, 2006

The CareGiver: Huperzine A Factsheet (Alzheimer's)

I recently read about Huperzine A. The following page contains a fact sheet about the herb. Huperzine A may have cognition-enhancing activity in some.

Source Huperzine A


Huperzine A is available from numerous manufacturers generically. Branded products include Memorall (PharmAssure), Huperzine Rx-Brain (Nature's Plus).


Huperzine A is a plant alkaloid derived from the Chinese club moss plant, Huperzia serrata, which is a member of the Lycopodium species. Huperzia serrata has been used in Chinese folk medicine for the treatment of fevers and inflammation.

Huperzine A has been found to have acetylcholinesterase activity. Huperzine B, also derived from Huperzia serrata, is a much less potent acetylcholinesterase inhibitor. Natural huperzine A is a chiral molecule also called L-huperzine A or (-)-huperzine A. Synthetic huperzine A is a racemic mixture called (±)-huperzine A. Huperzine A is also known as HUP, hup A and selagine. In Chinese medicine, the extract of Huperzia serrata is known as Chien Tseng Ta and shuangyiping. Huperzine A derivatives are being developed for pharmaceutical application.


Huperzine A may have cognition-enhancing activity in some.


Alzheimer's disease is a neurodegenerative disorder associated with neuritic plaques that affect the cerebral cortex, amygdala and hippocampus. There is also neurotransmission damage in the brain. One of the major functional deficits in Alzheimer's disease is a hypofunction of cholinergic neurons. This leads to the cholinergic hypothesis of Alzheimer's disease and the rationale for strategies to increase acetylcholine in the brains of Alzheimer's disease patients. Two FDA-approved drugs for the treatment of Alzheimer's disease, tacrine and donepezil, are acetylcholinesterase inhibitors.

Huperzine A is also an acetylcholinesterase inhibitor and has been found to increase acetylcholine levels in the rat brain following its administration. It also increases norepinephrine and dopamine, but not serotonin levels. The natural L or (-)-huperzine A is approximately three times more potent than the racemic or (±)-huperzine A in vitro.


There are limited pharmacokinetic studies with huperzine A. It appears that huperzine A is rapidly absorbed from the gastrointestinal tract and transported to the liver via the portal circulation. Some first-pass metabolism takes place in the liver, and huperzine A and its metabolites are distributed widely in the body, including to the brain. Following ingestion, the time to reach peak blood level is approximately 80 minutes.


Huperzine A has potent pharmacological effects and, particularly since long-term safety has not been determined, it should only be used with medical supervision. It may have some effectiveness in Alzheimer's disease and age-related memory impairment. It has been used to treat fever and some inflammatory disorders, but there is no credible scientific evidence to support these uses.


Numerous studies, most of them from China, suggest that huperzine A may be as effective as the drugs tacrine and donepezil in Alzheimer's disease. This is not so surprising since in vitro and animal model tests have demonstrated that huperzine A effectively inhibits acetylcholinesterase, an enzyme that catalyzes acetylcholine breakdown. Tacrine and donepezil work in the same way to conserve acetylcholine in the brain--the mode by which they presumptively improve memory and cognition in those with Alzheimer's and age-related cognitive impairment. Huperzine A may prove superior to tacrine (dose-limited due to its hepatotoxicity) if long-range studies, yet to be conducted, demonstrate its safety.

In one double-blind, randomized study, huperzine A, in injectable form, was tested against a saline control in 56 patients with multi-infarct dementia or senile dementia and in 104 patients with senile and pre-senile simple memory disorders. Huperzine A produced significant positive effects as measured by the Wechsler Memory Scale. Dizziness was experienced by a few of the huperzine A-treated patients.

In another study, this one multicenter, double-blind, placebo-controlled and randomized, 50 subjects with Alzheimer's disease were given huperzine A or placebo for eight weeks. Significant improvement was noted in 58 percent of the patients in terms of memory, cognitive and behavioral functions. Research is ongoing.


None known.


Huperzine A should be avoided by children, pregnant women and nursing mothers.

Because of possible adverse effects in those with seizure disorders, cardiac arrhythmias and asthma, those with these disorders should avoid huperzine A. Those with irritable bowel disease, inflammatory bowel disease and malabsorption syndromes should avoid huperzine A.


Adverse effects reported with huperzine A include gastrointestinal effects, such as nausea and diarrhea, sweating, blurred vision, fasciculations and dizziness. Possible adverse effects include vomiting, cramping, bronchospasm, bradycardia, arrhythmias, seizures, urinary incontinence, increased urination and hypersalivation.


Acetylcholinesterase Inhibitors: Use of huperzine A along with the acetylcholinesterase inhibitors donepezil or tacrine may produce additive effects, including additive adverse effects. Other acetylcholinesterase inhibitors include neostigmine, physostigmine and pyridostigmine, and use of these agents along with huperzine A may produce additive effects, including additive adverse effects.

Cholinergic Drugs: Use of huperzine A along with cholinergic drugs, such as bethanechol, may produce additive effects, including additive adverse effects.


Use of huperzine A with choline, phosphatidylcholine, CDP-choline and L-alpha-glycerylphosphorylcholine hypothetically might produce additive effects, including additive adverse effects.


There are no reports of overdosage with huperzine A.


There are various forms of huperzine A available, including extracts of Huperzia serrata, natural (-)-huperzine A and synthetic racemic (±)-huperzine A. Natural (-)-huperzine A is approximately three times more potent than the synthetic racemic mixture. The doses of natural (-)-huperzine A used in clinical studies ranged from 60 micrograms to 200 micrograms daily. Huperzine A should only be used with a physician's recommendation and monitoring.


Capsules — 50 mcg

Tablets — 50 mcg


Cheng DH, Tang XC. Comparative studies of huperzine A, E-2020 and tacrine on behavior and cholinesterase activities. Pharmacol Biochem Behav. 1998; 60:377-386.

Cheng DH, Ren H, Tang XC. Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport. 1996; 8:97-101.

Quian BC, Wang M, Zhou ZF, et al. Pharmacokinetics of tablet huperzine A in six volunteers. Chung Kuo Yao Li Hsueh Pao. 1995; 16:396-398.

Tang XC, Kindel GH, Kozikowski AP, Hanin I. Comparison of the effects of natural and synthetic huperzine A on rat brain cholinergic function in vitro and in vivo. J Ethnopharmacol. 1994; 44:147-155.

Xiong ZQ, Tang XC. Effect of huperzine A, a novel acetylcholinesterase inhibitor, on radial maze performance in rats. Pharmacol Biochem Behav. 1995; 51:415-419.

Xu SS, Gao ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition and behavior in Alzheimer's disease. Chung Kuo Yao Li Hsueh Pao. 1995; 16:391-395.

Ye JW, Cai JX, Wang LM, Tang XC. Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment. J Pharmacol Exp Ther. 1999; 288:814-819.

Zhang RW, Tang XC, Han YY, et al. Drug evaluation of huperzine A in the treatment of senile memory disorders. [Article in Chinese] Chung Kuo Yao Li Hsueh Pao. 1991; 12:250-252.