Author's Copy
Treatment
of Alzheimer disease and its
Clinical
Prospects Authors
Mohammad yusuf and Bahar Ahmed Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi-110062, Email:
[email protected] Maria Khan Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi-110062. Email:
[email protected]
This article appeared in a journal published by The Clinical Research Plus. The attached copy is furnished to the author for internal noncommercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding TCRP archiving and manuscript policies are encouraged to visit: http://www.tcrp.co.in
Cite this Article: Yusuf M, Khan M, Dubey V. Treatment of Alzheimer disease and its Clinical Prospects. The Clinical Research Plus. 2010;2:51-61.
Vaibhav Dubey Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Christian School of Pharmacy, Allahabad Agriculture Institute, Allahabad Uttar Pradesh-211007. Email:
[email protected]
A
lzheimer’s disease (AD) is one of the most common causes of dementia in the elderly, affecting at least thirty five million people world wide. It is now the fifth leading killer, which rose by 47% from 2000 to 2006. AD is defined as memory loss with at least one other area of cognitive impairment (e.g., language, attention, orientation, self-monitoring, judgment, motor skill, inability to perform daily activities). Generally loss of memory begins at about age of 65 and slowly progresses to severe impairment over 8 to 10 years, but it may occur sooner and advance at a different rate. Some prominent symptoms are language deficits, including word finding (especially nouns), comprehension, repetition, and fluency. Social graces, surprisingly, remain intact for a year, which eventually deteriorates to a loss of inhibition with periods of aggres-
Article
Article • •
Aluminum and mercury toxicity may contribute
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Thyroid disease
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Hydrocephalus
Physical inactivity
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Parkinson’s disease
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Lewy body dementia Sleep disorders
Sign and symptoms
sion or withdrawal. Personality and behavioral changes as well as problems in judgment occur with increasing severity as aging proceeds. Death usually occurs from malnutrition, heart disease, or infection. Clinical diagnosis cannot be definitively confirmed without autopsy.
Etiology The etiology of AD is unknown. Speculative causes include viruses, autoimmune disorders, accelerated aging process, and environmental contaminates, notably aluminum and aluminum-containing products.
Risk factors •
Family history- especially of epsilon 4 apolipoprotein (Apo) E gene on chromosome 19
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Advanced age (20% to 40% of those with fully developed symptoms of Alzheimer’s disease are over age 85)
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Temporal and spatial disorientation
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Cortical blindness
Diagnosis
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Extrapyramidal dysfunction
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Memory loss-eventually includes loss of personal information and inability to recognize family
Electroencephalogram and lumbar puncture— especially for rapid onset with delirium to rule out other causes
Accusatory behaviors
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Sleep study—to rule out sleep disorders
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Problems with sequential motor tasks
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Denial of symptoms
Mini Mental State Examination—measure of cognitive function
Levels of acetylcholine and A beta amyloid decrease and tau protein increases in CSF.
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Hallucinations, delusions, psychosis
Cholinergic transmitter deficiency and continual loss of cholinergic cells occur.
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Aggression, agitation, anxiety, restlessness
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Amyloid angiopathy is common
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Withdrawal, apathy
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Insomnia or disturbances in sleep/wake patterns
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Muscle rigidity
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Weight loss
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Incontinence
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Seizures
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Depression
Inability to perform daily activities
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Aphasia-language deficits including fluency, comprehension, word naming/finding
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Laboratory Test Tests such as complete blood count (e.g., for vitamin B12 or folate deficiency), chemistry battery (e.g., for chronic renal or liver failure), thyroid function tests, and others are done to rule out differential diagnoses. Testing of beta amyloid precursor protein levels in blood is still investigational but appears promising
Pathophysiology
Differential Diagnosis •
Depressive disorders
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Delirium through other causes
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Multi-infarct dementia
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Vitamin deficiency
Imaging
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Brain tumor
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Imaging is used to exclude other diagnoses such as neoplasms, hematomas, or infarcts.
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MRI or CT—detect diffuse cortical atrophy, including the hippocampus seen particularly as disease progresses; enlargement of sulci.
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EEG—normal or nonspecific slowing.
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Positron emission tomography (PET)—shows early metabolic changes in parietal cortex.
Female > male
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Drug intoxication, alcoholism
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Possibly head trauma, low education level, and environmental factors.
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Huntington’s disease
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Pick’s disease
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Down syndrome
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Stroke
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Oxidative stress > antioxidant reserve
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Creutzfeldt-Jakob disease
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Glutamate excess
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Advanced syphilis
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and Apo E; which accumulates in the cerebral blood vessel walls; testing of Apo E is controversial, however Apo E epsilon 4/4 homozygotes diagnose AD at about 97% accuracy
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AD is diagnosed on clinical grounds and by ruling out all other possible causes. A thorough evaluation includes neuropsychologic testing, EEG, chest radiograph, and a CBC.
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Diffuse atrophy of the cerebral cortex; secondary enlargement of the ventricular system
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Neurofibrillary tangles (first noted by Alzheimer) in neuronal cytoplasm
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Neuritic plaques—containing A beta amyloid
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Article
Article fective for some patients in the early to middle stages.
The four FDA-approved cholinesterase inhibitors are: Razadyne® Generic name: galantamine Year approved by the FDA: 2001 Indications: Early to moderate Alzheimer’s disease Mechanism of Action: Razadyne® prevents the breakdown of acetylcholine and stimulates nicotinic receptors to release more acetylcholine in the brain. Side Effects: Nausea, vomiting, diarrhea, weight loss Miscellaneous: This medication was formerly known as Reminyl®.
Treatment and therapy of Alzheimer disease
few months to a few years. Donepezil can be used for severe AD, too. Another drug, memantine (Namenda®), is used to treat moderate to severe AD. However, these drugs don’t stop or reverse AD and appear to help patients only for months to a few years by maintaining memory, thinking, and speaking abilities and may help with certain behavioral problems. These drugs work by regulating neurotransmitters. Other medicines may ease the behavioral symptoms of AD-sleeplessness, agitation, wandering, anxiety, anger, and depression. Treating these symptoms is comforting for the patients.
There is no proven treatment to stop AD. For people with mild or moderate AD, donepezil (Aricept®), rivastigmine (Exelon®), or galantamine (Razadyne®) may help to maintain cognitive abilities and help to control certain behavioral symptoms for a
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No published study directly compares the four approved AD drugs. Because they work in a similar way, it is not expected that switching from one of these drugs to another will produce significantly different results. However, an AD patient may respond better to one drug than to the other.
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Acetylcholinesterase Inhibitors Those suffering from Alzheimer’s disease have low levels of acetylcholine, an important brain chemical involved in nerve cell communication. There are four drugs, called cholinesterase inhibitors, approved by the Food and Drug Administration (FDA) that are designed to regulate AD’s symptoms and delay its course. Cholinesterase inhibitors slow down the metabolic breakdown of acetylcholine, and make more of this chemical available for communication between cells. Although, there is no cure for Alzheimer’s disease, however, these drugs helps in slowing the progression of cognitive impairment and can be ef-
The Clinical Research Plus
Exelon® Generic name: rivastigmine Year approved by the FDA: 2000 Indications: Early to moderate Alzheimer’s disease Mechanism of Action: Exelon® prevents the breakdown of acetylcholine and butyrylcholine (a chemical similar to acetylcholine) in the brain. Side Effects: Nausea, vomiting, weight loss, upset stomach, weakness. In 2007, FDA approved the Exelon®Patch (rivastigmine transdermal system) to deliver this medication through a skin patch as an option to the oral capsule. Aricept® Generic name: donepezil Year approved by the FDA: 1996 Indications: Early, moderate and severe Alzheimer’s disease Mechanism of Action: Aricept® prevents the
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Article breakdown of acetylcholine in the brain. Side Effects: Nausea, diarrhea, vomiting Aricept may also have a limited slowing effect on the progression from mild cognitive impairment (MCI) to AD. Study results published in April 2005 by the New England Journal of Medicine indicated that over the first year of a three-year trial, those with MCI treated with Aricept had a reduced risk of progressing to AD compared to participants who took vitamin E or a placebo (an inactive pill). However, by the end of the study, there was no difference among the three groups except for those with the ApoE4 gene. Aricept’s effect lasted up to two to three years in those participants. Previous studies have indicated those with the ApoE4 gene have a higher chance of developing AD than the general population. Cognex® Generic name: tacrine Year Approved by the FDA: 1993 (Cognex is still available but no longer actively marketed by the manufacturer, due to the severe side effects.) Indications: Early to moderate Alzheimer’s disease Mechanism of Action: Cognex prevents the breakdown of acetylcholine in the brain. Side Effects: Nausea, diarrhea, possible liver damage
Selegiline A number of studies have examined evidence for the use of Selegiline (Eldepryl), a selective monoamine oxidase inhibitor, in the treatment of Alzheimer’s disease. Most of these studies have shown some improvement in cognition, behavior, and mood, but little evidence of a global benefit in cognition, functional ability, and behavior. In 2000, the authors of a meta-analysis of 15 clinical trials concluded that there was not enough evidence to recommend selegiline as a treatment for Alzheimer’s disease. Because of the risk of stupor, rigidity, severe agitation, and elevated temperature, selegiline therapy is contraindicated in patients who are taking mep-
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Article eridine (Demerol), and this precaution often is extended to other opioids. Concurrent use of selegiline with tricyclic antidepressants and selective serotonin reuptake inhibitors also should be avoided. These restrictions may limit the use of Selegiline in patients with Alzheimer’s disease.
Anti-Inflammatory Drugs Inflammation surrounding α-amyloid plaques which results in destruction of neurons is thought to be a key factor in the pathogenesis of Alzheimer’s disease. Observational studies have found that persons who regularly use nonsteroidal anti-inflammatory drugs (NSAIDs) have a decreased incidence of Alzheimer’s disease. Thus, NSAIDs likely have some neuroprotective effect.
Rivastigmine (Exelon)
Acetylcholinesterase inhibitor Butyrylcholinesterase inhibitor
Start at 1.5 mg twice daily, taken with food; at 2-week intervals, increase each dose by 1.5 mg, up to a dosage of 6 mg twice daily.
6 mg twice daily
3 mg twice daily
Galantamine (Reminyl)
Acetylcholinesterase inhibitor Nicotinic receptor actions
Start at 4 mg twice daily with food; at 4-week intervals, increase each dose by 4 mg, up to a dosage of 12 mg twice daily.
12 mg twice daily
8 mg twice daily.
Claims Made for Acetylcholinesterase Inhibitor Therapy in Alzheimer’s disease Claim
Evidence
Comments
Improves cognition
All 24-to 26-week clinical trials showed statistically significant benefit in the ADAS-cog and MMSE. About 30 to 60 percent of treated patients had a 4-point ADAS-cog improvement compared with those who received placebo; average improvement in MMSE was 1 point. Cognitive benefits were sustained over 1 to 2 years.
Study populations were highly selected; patients with significant comorbid conditions were excluded.
Improves global impressions
In the 24- to 26-week trials, 20 to 40 percent of patients were thought to have improved.
Stabilization or less-than-expected deterioration would not be evident to a physician.
Improves functional ability
Results in the 24to 26-week trials were contradictory. A subsequent, industry-sponsored trial showed sustained benefit of donepezil (Aricept) therapy given for 1 year.
Because functional ability is likely to be related to physical ability and psychological health and cognition, the exclusion of frail and ill patients from the trials may give a greater impression of benefit.
Delays nursing home placement
One trial of tacrine (Cognex) showed a reduced risk of nursing home placement. Statistical extrapolations from completed trials of donepezil showed a 12- to 21month delay.
The tacrine trial had strict inclusion criteria; the donepezil trials also involved a highly selected population.
Improves disturbed behaviors
A galantamine (Reminyl) trial reported statistically significant improvement in NPI. A subsequent trial of donepezil suggested benefit.
Excluding patients with severe behavior disorders or minimizing the number of such patients in a trial may result in overstatement of the benefits of drug therapy.
Alzheimer’s Vaccine Scientists have succeeded in eradicating many deadly diseases through vaccination, and same approach might prevent or cure Alzheimer’s disease. A build up of beta amyloid protein in the brain plays an important role in Alzheimer’s disease. Thus, prevention or clearing of the protein accumulation could be an effective treatment. In 1999, studies revealed that injection of the beta amyloid itself, called active immunization, caused laboratory mice to produce antibodies against the protein and reduced its accumulation. Spurred on by the potential of immunotherapy, some pharmaceutical companies started clinical trials. In 2001, Elan and Wyeth began actively immunizing over 300 Alzheimer’s patients with beta amyloid. The trials were halted in 2002
Acetylcholinesterase Inhibitors used in the Treatment of Alzheimer’s disease Drug
Pharmacologic actions
Dosage
Target dosage
Minimum therapeutic dosage
Donepezil (Aricept)
Acetylcholinesterase inhibitor
Start at 5 mg once daily, taken at bedtime; after 6 weeks, increase to 10 mg once daily.
10 mg once daily
5 mg daily
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when about six percent of participants developed a potentially serious side effect, acute encephalitis (inflammation in the brain). Several participants later died from other causes. Autopsies revealed that a large amount of beta amyloid had been cleared from their brains, their brain volume was lower, and lower levels of tau, another protein related to Alzheimer’s disease, were found in their spinal fluid. Further, for the living trial participants who developed antibodies, there was evidence of better memory, attention and concentration. In 2007, further human trials testing the efficacy and safety (Phase II) of passive immunotherapy were initiated. In passive immunotherapy, antibodies to a protein rather than the protein itself are given to the recipients. By using this form, researchers believe they can avoid the side effects that resulted from earlier trials of the active vaccination. Phase III clinical trials that will involve more participants are also planned.
Active immunotherapy The most advanced such active vaccine, called aac001, is a modified version of AN-1792, and is intended to trigger the natural antibodies for beta-Amyloid. One A-α vaccine was found to be effective against inclusion body myositis in mouse models.
Passive immunotherapy Also derived from the AN-1792 immunotherapy program. The most advanced such candidate is known as bapineuzumab or aab-001, and this antibody is designed as essentially identical to the natural antibody triggered by the earlier AN-1792 vaccine. The aab-001 antibody is in Phase 3 clinical trials for both Apolipoprotein E4 gene carriers, and Apolipoprotein E4 gene non-carriers.
Statins Several clinical trials are underway to test whether various types of statins (cholesterol-lowering drugs) can help slow the progression of Alzheimer’s disease. Past studies have produced conflicting results, June - 2010
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Article selective amyloid beta 42 lowering agent. It reduces the production of the toxic amyloid beta in favor of shorter forms of the peptide. Negative results were announced regarding tarenflurbil in July 2008 and further development was canceled.
Metal-protein interaction attenuation
and further clinical trials will be necessary before any statin therapy is recommended. In 2007, researchers at the Boston University School of Medicine examined data from the U.S. Veterans Affairs Medical System, and found that a statin called Zocor® (simvastatin) appeared to reduce the incidence of Alzheimer’s. However, in January 2008, data obtained from Catholic clergyman by scientists at the Rush University Medical Center showed no relationship between statins and cognitive decline. In April 2008, Pfizer, a pharmaceutical company that manufactures Lipitor® (atorvastatin calcium), reported no significant difference between clinical trial participants given Lipitor and Aricept®, and those given Aricept and a placebo.
Estrogen Research suggests that estrogen taken to manage the symptoms of menopause may also protect the brain. Therefore, scientists have been interested in knowing whether estrogen could reduce the risk or slow the advance of Alzheimer’s. However, clinical trials of those already diagnosed with the disease, showed that estrogen had no impact on its progression. Other studies indicate that women who begin using estrogen after age 60 to 65 are at an increased risk of developing dementia, as well as heart attack and stroke. Estrogen is now only recommended for short term use to treat menopausal symptoms. Recent research has helped to clarify the neuroprotective role of estrogen which is taken by younger 58
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women before menopause. According to a study published in August 2007, scientists from the Mayo Clinic found that women who had one or both ovaries removed prior to menopause had an increased long-term risk of dementia or cognitive impairment. However, those who underwent ovary removal, but also had estrogen treatment until at least age 50 did not experience this higher risk. These findings suggest that if taken before menopause, the neuroprotective benefits of estrogen may outweigh the risks of side effects, such as heart problems, stroke and cognitive impairment.
Omega-3 Fatty Acids Omega-3 fatty acids are found mainly in “oily” fish such as salmon and albacore tuna, but are also present in certain nuts and oils. Scientists believe they may have a protective effect on the brain. Clinical trials are underway to test whether these fatty acids can slow both the cognitive and functional decline in those with mild to moderate Alzheimer’s.
Gamma secretase inhibition Gamma secretase is a protein complex thought to be a fundamental building block in the development of the amyloid beta peptide. A gamma secretase inhibitor known as LY451039 is in Phase 3 trials.
Gamma secretase modulation Tarenflurbil (MPC-7869, formerly R-flubiprofen) is a gamma secretase modulator sometimes called as The Clinical Research Plus
PBT2 is an 8-hydroxy quinoline that removes copper and zinc from cerebrospinal fluid, which are apprehended to be necessary catalysts for amyloid beta aggregation. This drug has been in a Phase II trial for early Alzheimer’s and which has been reported preliminarily promising.
Methylthioninium chloride In July 2008, researchers announced positive results from methylthioninium chloride (MTC), (trade name: rember) a drug that dissolved Tau polymers. Phase II results indicated that, it is the first therapy that succeeded in modifying the course of disease in mild to moderate AD.
Dimebon In July 2008 antihistamine that was formerly available in Russia, Dimebon was given to a group of AD patients. The group receiving Dimebon improved somewhat over the 6 months of the study (and this continued for the next six months), whereas those on placebo deteriorated. Unfortunately the consecutive phase-III trial failed to show significant positive effects in the primary and secondary endpoints. The sponsors acknowledged in March 2010 that initial results of the phase III trial showed that while the drug had been well tolerated, its outcomes did not significantly differ from the placebo control.
Antibiotic therapy Only one clinical trial is being done (at McMaster University) to investigate the efficacy of antibiotic therapy. The authors of the study indicated that it was effective in delaying the progress of the disease: “In conclusion, a 3-month course of doxycycline and rifampin reduced cognitive worsening at 6 months of
The Clinical Research Plus
follow-up in patients with mild to moderate AD.” A re-examination of the same data using: “AUC analysis of the pooled index showed significant treatment effect over the 12-month period”. Several studies using minocycline and doxycycline, in an animal model of Alzheimer’s disease, have indicated that minocycline and doxycycline exerts a protective effect in preventing neuron death and slowing the onset of the disease.
Antiviral therapy The possibility that AD could be treated with antiviral medication is suggested by a study showing collocation of herpes simplex virus with amyloid plaques.
Angiotensin receptor blockers A retrospective analysis of five million patients recorded by the US Department of Veterans Affairs system found that different types of commonly used anti-hypertensive medications had very different AD outcomes. Those patients taking angiotensin receptor blockers (ARBs) were 35-40% less likely to develop AD than those using other anti-hypertensives.
Cannabinoids Treatments that target the endocannabinoid system may have a place in the treatment of AD, although research is still incipient.
Allopregnanolone Allopregnanolone has been identified as a potential drug agent. Levels of neurosteroids such as allopregnanolone decline in the brain in old age and in AD. Allopregnanolone has been shown to aid the neurogenesis that reversed cognitive deficits in a mouse model of AD.
Insulin sensitizers Recent studies suggests that an association between insulin resistance and AD (sensitivity to insulin can decline with aging): In a clinical trial, certain insulin
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Article sensitizer called “Rosiglitazone” improved cognition in a subset of AD patients; it vitro, beneficial effects of Rosiglitazone on primary cortical rat neurons have been demonstrated.
Essential Nutrients •
Vitamin E (400 to 800 IU/day), vitamin C (1,000 mg tid), and coenzyme Q10 (50 mg tid) protects against oxidative stress.
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Acetyl-L-carnitine (1,000 to 1,500 mg/day) improves energy metabolism of brain tissue and neurotransmitter activity.
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Phosphatidyl serine (100 mg bid to tid) facilitates membrane receptor activities and improves cognition and mood.
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NADH (10 mg/day) stimulates biosynthesis of dopamine and noradrenaline.
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Vitamin B12 (1,000 mcg/day) and folic acid (800 to 1,000 mcg/day) may improve cognitive function even in the absence of abnormal serum values. Vitamin B1 (300 to 2,000 mg daily) and zinc (45 mg daily) are also beneficial.
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Melatonin—investigational for insomnia; 1 to 2 mg before bed, or 3 to 10 mg daily.
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Antioxidants—vitamin E (1,000 IU bid) and selegiline (not FDA approved for Alzheimer’s) may slow progression of AD.
Herbal therapy Herbs may be used as dried extracts (pills, capsules, or tablets), teas, or tinctures (alcohol extraction, unless otherwise noted). Dose is 1 heaped tsp. herb/cup water steeped for 10 minutes (roots need 20 minutes). •
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Ginkgo biloba (120 mg bid, standardized to 24% ginkgo flavone glycosides and 6% terpene) increases cerebral circulation and regulates platelets. Monitor carefully with concurrent use of anticoagulants. Combine the following in equal parts to enhance peripheral circulation and improve mood: gotu kola (Centella asiatica), rosemary (Rosemarinus officinalis), hawthorn (Crataegus monogyna), prickly ash bark (Xanthoxylum clava-herculis),
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Article passionflower (Passiflora incarnata), and lavender (Lavendula angustifolia). For anxiety, substitute kava (Piper methysticum) for lavender. For depression, substitute St. John’s wort (Hypericum perforatum) for lavender. Take 30 to 60 drops tincture bid to tid, or drink one cup of tea tid.
Homeopathy Acute dose is three to five pellets of 12X to 30C every one to four hours, until symptoms resolve. Remedies to consider include the following: • Alumina for mental dullness with slowed speech and loss of identity • Argentum nitricum for poor memory with impulsivity, anxiety, depression, and compulsive thoughts or behavior. • Cocculus for slowed mentation with grief and vertigo • Conium for progressive mental deterioration with emotional flatness • Helleborus for stupefaction with indifference to the outside world alternating with anguish and incomprehension • Zincum for confusion with slowed speech, use of incorrect words, and suicidal thoughts • Anacardium for cruel behavior, cursing, memory loss
Prevention • NSAIDs—very preliminary studies indicate that they may lower risk; potentially serious side effects at necessary doses and duration • Estrogen use for women—trials indicate it may lower risk of getting AD; potentially serious side effects • Reducing aluminum and mercury exposure may be helpful. Chelation for aluminum with desferrioxamine slows progression compared to controls. • Clinical trials (many already begun and some well advanced) will test the following, and hopefully within the next five to seven years the most promising of them will be approved for people The Clinical Research Plus
with Alzheimer’s disease: • Drugs that block the enzymes that split off the toxic A-beta from APP (secretases inhibitors). • Drugs that prevent the threatening clumping together of newly formed A-beta molecules. • Drugs (like Neprilysin) that help clear away the accumulating A-beta molecules before they begin clumping together. • “Neuroprotective” drugs (like the growth factors) that increase the ability of threatened nerve cells to stay alive. • Drugs that will prevent the chemical modification of tau protein, and so prevent tangles. • New vaccines that will eliminate both the production and the accumulation of amyloid (A-beta) but not have the dangerous side effects of the first vaccines. • New vaccines that will eliminate tangles. • Improved techniques to implant genetically engineered living cells into the brain for delivery of growth factors and other drugs to counteract the development of plaques and tangles. • New anti-diabetic drugs that will correct glucose metabolism in the brains of people with Alzheimer’s disease. • New drug delivery techniques which will ensure that drugs get to the regions of the brain where they are needed. • Drugs that block the enzymes that split off the toxic A-beta from APP (secretases inhibitors). • Drugs that prevent the threatening clumping together of newly formed A-beta molecules. • Drugs (like Neprilysin) that help clear away the accumulating A-beta molecules before they begin clumping together. • “Neuroprotective” drugs (like the growth factors) that increase the ability of threatened nerve cells to stay alive. • Drugs that will prevent the chemical modification of tau protein, and so prevent tangles. • New vaccines that will eliminate both the pro-
The Clinical Research Plus
duction and the accumulation of amyloid (A-beta) but not have the dangerous side effects of the first vaccines. • Improved availability of non-invasive imaging techniques that will reveal plaques and tangles even before dementia develops. Special chemicals are injected into the blood that reach the brain and attach to plaques. These are visualized by imaging, so facilitating early diagnosis and revealing whether treatment strategies are reducing the brain abnormalities. • New biological markers for Alzheimer’s disease that can be measured in the blood, in the CSF, in urine, and in the skin, to help in early diagnosis, and in evaluation of treatment therapies. • Early diagnosis based on the pattern of brain waves (EEG). • New cognitive training regimens will help slow down the decline in brain functioning without the use of drugs. • Delivery of therapeutic agents via the nose, in some instances associated with harmless viruses called “phages”. < (References on demand)
Authors Mohammad yusuf and Bahar Ahmed
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi-110062, Email: yusuf4682@ gmail.com
Maria Khan
Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi-110062. Email:
[email protected]
Vaibhav Dubey
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Christian School of Pharmacy, Allahabad Agriculture Institute, Allahabad Uttar Pradesh-211007. Email:
[email protected]
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