Treatment for Alzheimer's Disease: Neurological & surgical interventions

Gene Therapy

September 2005

Targeting a key enzyme with gene therapy reversed course of Alzheimer's disease in mouse models

A study using genetically engineered mice has reversed the rats' memory loss by silencing a gene that helps produce amyloid plaques. The size and number of plaques were reduced by two-thirds within a month.
The report appeared in the October 1 issue of Nature Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2005-09/si-tak092005.htm

April 2005

Gene therapy slows cognitive decline in trial

The first human clinical trial of gene therapy for Alzheimer’s, involving 8 volunteers, has found an increase in the brain’s use of glucose — a sign of brain activity — and a significant slowing of the patients’ rate of cognitive decline in the 6 patients who completed the procedure safely.
The study was published online on April 24 in Nature Medicine. Full reference
http://www.eurekalert.org/pub_releases/2005-04/uoc--acd041805.htm

September 2004

New gene therapy technique

A new technique using gene therapy to deliver nerve growth factor into regions of the brain where neurons are degenerating is being trialed in a two-year study. The technique, which requires neurosurgery to inject the drug precisely where it is required (the basal forebrain), uses a new drug called CERE-110. Extensive studies in several animal models, including primates, have showed that NGF gene delivery to the basal forebrain prevented the death of cholinergic neurons (which undergo severe degeneration and death in Alzheimer's disease patients).
http://www.eurekalert.org/pub_releases/2004-09/rpsl-seg092004.htm

April 2004

Preliminary results promising in Alzheimer's gene therapy trial

A small, preliminary study has had some success in delaying brain cell loss in early Alzheimer’s patients through the surgical placement of genetically modified tissue directly into their brains.
The study was reported on April 27 at the American Academy of Neurology meeting in San Francisco.
http://www.eurekalert.org/pub_releases/2004-04/uoc--pra042204.htm

April 2001

UCSD team performs first surgery in gene therapy protocol for Alzheimer's disease

In a groundbreaking procedure, physicians at the University of California, San Diego (UCSD) School of Medicine have surgically implanted genetically modified tissue into the brain of an Alzheimer's patient. This launches the first phase of an experimental gene therapy protocol for Alzheimer's disease. The therapy delivers a natural molecule called nerve growth factor (NGF) to the dying cells in the brain.
If the protocol is successful, implanted cells could begin to affect brain function in a month or two, but Tuszynski cautions that "it may take several years to test the procedure in a large enough number of patients to determine whether it will be useful therapy." The therapy is not expected to cure Alzheimer's disease, but it may restore some brain cells and alleviate symptoms such as short-term memory loss for several years.
This research was reported in the Feb. 12 issue of Proceedings of the National Academy of Science.
http://www.eurekalert.org/pub_releases/2001-04/UNKN-Utpf-0904101.htm

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CSF shunt

August 2004

Draining toxins from cerebrospinal fluid stabilizes cognitive decline

The ever-slowing capacity to clear the build-up of such toxins as isoprostanes and misfolded proteins that accumulate in the brains of Alzheimer's disease patients causes the death of cells involved in memory and language. A preliminary study has shown that reducing the levels of isoprostanes by draining cerebral spinal fluid can stave off future reductions in cognitive abilities. Cognitive scores in the 8 patients receiving the treatment were stable after one year, while scores in those not receiving the treatment declined 20%. The next phase of the study involves nearly 100 patients.
The study appeared in the August issue of the Journal of Alzheimer's Disease. Full reference
http://www.eurekalert.org/pub_releases/2004-08/uopm-dti082004.htm

October 2002

Can Alzheimer's disease be slowed by shunting cerebrospinal fluid?

A pilot study has tested the hypothesis that improving cerebrospinal fluid (CSF) turnover will slow or stop the progression of dementia in people with Alzheimer's disease. CSF shunting for dementia, described in 1969, was largely abandoned due to mixed clinical results and an unacceptably high incidence of adverse events. However recent clinical studies in which CSF shunting was used to treat patients with symptomatic hydrocephalus demonstrated a coincidental lack of cognitive decline in patients who also had Alzheimer's dementia. A pilot study has found Alzheimer's patients who were shunted experienced relative stability while the control group demonstrated a fairly robust decline in cognitive function over the 12 months of the study. A larger, multi-center, controlled clinical trial is now underway.
The study appeared in the October 22 issue of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2002-10/aaon-cad101502.htm

March 2002

Possible new surgical treatment

An 18-month, double-blind placebo study into a new surgical treatment for Alzheimer’s disease using a device called the COGNIShunt, is being undertaken by neurologists at Emory University. The shunt is designed to drain cerebrospinal fluid (CSF) from the skull and into the abdominal cavity. By reducing the build-up of CSF around the brain, doctors hope this device will help to stabilize the disease. In a pilot study of the COGNIShunt, the device was well tolerated by individuals with mild to moderate Alzheimer’s disease.
http://www.eurekalert.org/pub_releases/2002-03/euhs-esc032102.htm

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Animal studies

December 2006

New way to target Alzheimer's disease

In a series of studies in transgenic mice, a synthetic peptide designed to block the interaction between apolipoprotein E and amyloid-beta protein reduced the aggregation of toxic amyloid protein in the brain by around 50%. The treated mice showed no memory decline.
The study was published in the December 5 issue of the Proceedings of the National Academy of Sciences. Full reference
The full text is available at http://www.pnas.org/cgi/content/full/103/49/18787 http://www.eurekalert.org/pub_releases/2006-12/nyum-sda120406.htm

Androgen therapy may slow progress of Alzheimer's disease

Recent studies have suggested a link between testosterone loss in men and Alzheimer’s. A new study has now found a correlation between low testosterone and elevated beta-amyloid, providing more support that testosterone depletion in aging men increases the risk of Alzheimer’s. Testosterone belongs to a group of steroid hormones called androgens. The mouse study found that androgen therapy was successful in preventing beta-amyloid accumulation and cognitive decline in castrated mice.
The findings were published in the December 20 issue of The Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2006-12/sfn-tm121906.htm

September 2006

Insulin receptor stops progression of Alzheimer's

Following previous research suggesting Alzheimer's might be a brain-specific neuroendocrine disorder, or a Type 3 diabetes, a new study has found that stimulation of a receptor in the brain that controls insulin responses prevents several components of neurodegeneration and preserves learning and memory in rats with induced Alzheimer's disease, raising the possibility that patients in the very early stages of Alzheimer’s might be treatable.
The study appeared in the September issue of the Journal of Alzheimer's Disease. Full reference
http://www.eurekalert.org/pub_releases/2006-09/l-irs092106.htm

August 2006

Brain enzyme treatment for Alzheimer's

In a new approach to treating Alzheimer’s, increasing brain levels of ubiquitin C-terminal hydrolase L1 (Uch-L1) — an enzyme that helps neurons rid themselves of excess or aberrant proteins — has restored a great deal of brain activity to mice with Alzheimer's symptoms. The enzyme Uch-L1 is part of a network that controls a memory molecule called CREB, which is inhibited by amyloid beta proteins in people with Alzheimer's. Uch-L1 is found at reduced levels in the Alzheimer's brain. As well as improving memory in genetically engineered mice, treatments that restored Uch-L1 levels corrected deficits in nerve transmission both in brain slices treated with amyloid-beta and in slices taken from transgenic mice.
The report appeared in the August 25 issue of Cell. Full reference
http://www.eurekalert.org/pub_releases/2006-08/cp-bet082106.htm
http://www.eurekalert.org/pub_releases/2006-08/cumc-crr082206.htm

Why chances of Alzheimer's increase with age

Experiments with roundworms have revealed two important proteins that help slow down the accumulation of amyloid-beta. HSF-1 breaks apart amyloid and disposes of it — but aging slows HSF-1, so it can't keep up. DAF-16 helps it out, by clumping extra amyloid together in a way that makes it less toxic. The finding supports recent research indicating amyloid clumps, or plaques, are not the main problem, rather, smaller amyloid tendrils inside cells are. The study also explains why aging increases the likelihood of Alzheimer’s. Most importantly of all, it suggests a new approach to treating Alzheimer’s.
The report was published online 10 August in Science Express, and in the 15 September issue of Science. Full reference
http://www.msnbc.msn.com/id/14290153/
http://www.boston.com/news/nation/articles/2006/08/11/scientists_find_natural_alzheimers_controls/

May 2006

Potential new treatment strategy for Alzheimer's

A study has identified several new compounds that could play a role in preventing or treating Alzheimer's disease and other degenerative conditions of the nervous system. In culture, these compounds bind with a receptor called p75NTR; a receptor that in the body binds neurotrophins. There is some evidence that in Alzheimer's, some of the neurons that die express the p75NTR binding site, indicating they may be dying because neurotrophins are binding to them. Because the new compounds bind with p75NTR in place of neurotrophins, they may provide a means of preventing damage that neurotrophins would otherwise be causing. The compounds were also found to inhibit the death of oligodendrocytes.
The study appeared in the May 17 issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2006-05/uoc--pnt051706.htm

July 2005

Memory loss in genetically engineered mice reversed

Mice were genetically engineered to develop dementia; the transgene was designed to be able to be turned off. The researchers expected that when the transgene expressing the dementia was turned off, memory loss would stop. Instead, they were surprised to find the loss was reversed; the mice regained their memory. A further surprise occurred when it was found that the neurofibrillary tangles, thought to be one of the causes of dementia, remained, and even increased, suggesting that the tangles are not a cause of dementia.
The results were published in the July 15 issue of Science. Full reference http://www.eurekalert.org/pub_releases/2005-07/uom-uom071105.htm

October 2004

Inhibiting Apolipoprotein E possible means of therapeutic intervention

It has been known that the inflammatory protein ApoE can speed the buildup in the brain of amyloid plaques,but the mechanism has not been known. A mouse study found ApoE is responsible for converting harmless amyloid-beta into the toxic fibrous deposits known as filamentous amyloid. This process is needed to damage nerve cells in parts of the brain controlling memory and cognition. Mice with Alzheimer's disease showed memory deficits only when the ApoE gene was present. The study suggests that preventing ApoE from acting upon amyloid-beta may prove to be an effective means of therapeutic intervention.
Two papers have been published in the October 2004 issues of the Journal of Alzheimer's Disease and the Neurobiology of Aging. Full reference 1, 2
http://www.eurekalert.org/pub_releases/2004-10/uosf-rur102904.htm

Researchers identify brain protein that halts progression of Alzheimer's

Researchers have identified a protein in the brain, "transthyretin," that halts the progression of Alzheimer's disease in human brain tissue by blocking beta-amyloid.
The findings were presented on October 26 at the 34th annual meeting of the Society for Neuroscience in San Diego, Calif.
http://www.eurekalert.org/pub_releases/2004-10/nioe-rib102504.htm

Early clinical treatment can halt progression of Alzheimer's disease

A study using genetically engineered mice has provided evidence that early clinical treatment of brain lesions (by injecting anti-beta-amyloid antibodies into the hippocampus) can halt the progression of Alzheimer's disease. The clearance of amyloid plaques led to the clearance of the lesions caused by neurofibrillary tangles. The effect on neurofibrillary tangles only occurs, however, if done at a particular stage of the tangle’s growth — the earlier the treatment begins, therefore, the better the chance of success. The demonstration that early treatment of amyloid plaques stops the progression of Alzheimer’s provides support for the controversial theory that the accumulation of amyloid plaques is the initiating trigger of the disease process.
The findings are reported in the August 5 issue of Neuron. Full reference
http://www.eurekalert.org/pub_releases/2004-08/uoc--ect072804.htm

June 2003

Buildup of amyloid plaques linked to gene inhibition

Examination of genetically engineered mice and of brain tissue from deceased Alzheimer's patients has found that the buildup of amyloid plaques in the brain dramatically inhibits six genes known to be important for the formation of new memories. The finding suggests a new approach to the treatment of Alzheimer’s disease, combining amyloid-lowering treatment with other strategies designed to block the effect of amyloid on these genes.
The results were reported in the June 15 issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2003-06/uosf-sla062503.htm

April 2003

A new approach to slowing the progression of Alzheimer’s

Researchers have discovered the molecules that play a critical role in making the brain think it is under attack from the amyloid plaques characteristic of Alzheimer’s disease. Microglial cells detect beta amyloid plaques and gear up to fight them as foreign invaders. However, for some unknown reason, they don’t follow through on the attack, but remain inflamed. It is this inflammation that causes a lot of the problem. Research has now shown that the microglial cells at least four different receptor proteins to bind to the amyloid. Each one of these receptor proteins act together at the same time to drive the inflammation. This discovery suggests a new approach to treating Alzheimer’s — finding a means to block these receptors.
The study was published in the April issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2003-04/cwru-mti042903.htm

March 2003

Gene transfer reduces levels of key Alzheimer's disease protein

An animal study has found that a molecule that naturally degrades of the protein beta-amyloid (the substance in the amyloid plaques indicative of Alzheimer’s) appears to reduce the levels of that protein by nearly 50% when delivered by gene therapy.
The findings appear in the March 15 issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2003-03/si-gtr032003.htm

September 2001

Growth factor creates new neurons; may aid treatment of neurological diseases

In a series of studies, a growth factor (BDNF) was introduced into the adult rat brain, and was found to produce new neurons in various brain regions. BDNF is reduced in parts of the brain of those with Huntington’s disease and Alzheimer’s disease. These studies indicate that supplementing the adult brain with BDNF not only supports neurons in those brains, but also induces new neurons from precursor cells.
The studies were reported in the September 1 issue of The Journal of Neuroscience.
http://www.eurekalert.org/pub_releases/2001-08/sfn-nnm083101.htm

April 2001

Transplanted human neural stem cells improve memory in rats

Laboratory-grown human neural stem cells, the building blocks of the brain, were successfully transplanted for the first time into the brains of aged rats and dramatically improved the animals' cognitive function. The results of the study could lay the foundation for new treatments in diseases such as Alzheimer's and Parkinson's.
Neural cell transplant studies recently suffered a setback when transplanted fetal cells worsened symptoms in Parkinson's patients. However, such fetal cells are already differentiated. Laboratory-grown stem cells are not differentiated, allowing the host brain to take over, dictating where the stem cells should migrate and what types of cells they should become. As a result, the transplanted cells became functionally integrated into the neuronal circuitry of the host animal. Postmortem examination of the rats' brains demonstrated that the transplanted human brain cells had not only differentiated and were thriving in the new environment, but that the rats' own neuronal fibers had grown dramatically in areas associated with spatial memory.
The findings are reported in the May 1 edition of NeuroReport, a fully refereed online journal.
http://www.eurekalert.org/pub_releases/2001-04/UoIa-Thns-2304101.htm

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