Navigation Links
Alzheimer's cognitive decline slowed

PET scans and cognitive tests have suggested that Alzheimer's disease patients with genetically modified tissue inserted directly into their brains show a reduction in the rate of cognitive decline and increased metabolic activity in the brain, according to a study published in the April 24, 2005 online issue of the journal Nature Medicine by researchers at the University of California, San Diego (UCSD) School of Medicine.

PET scans demonstrated an increase in the brain's use of glucose, an indication of increased brain activity, while mental-status tests showed a slowing of the patients' rate of cognitive decline was reduced by 36 to 51 percent. In addition, researchers examined the brain tissue of a study participant who had died and found robust growth of extensions from the dying cholinergic cells near the site of growth factor gene delivery. Cholinergic neuron loss is a cardinal feature of Alzheimer's disease, a progressive brain disorder affecting memory, learning, attention and other cognitive processes.

"If validated in further clinical trials, this would represent a substantially more effective therapy than current treatments for Alzheimer's disease," said Mark Tuszynski, M.D., Ph.D., UCSD professor of neurosciences, neurologist with the VA San Diego Healthcare System, and the study's principal investigator. "This would also represent the first therapy for a human neurological disease that acts by preventing cell death."

In this first-ever gene therapy for Alzheimer's disease, UCSD physician-scientists took skin cells from eight patients diagnosed with early Alzheimer's disease. The tissue was modified in the lab to express nerve growth factor (NGF), a naturally occurring protein that prevents cell death and stimulates cell function. In surgeries that took place in 2001 and 2002 at UCSD's John M. and Sally B. Thornton Hospital, the genetically modified tissue was implanted deep within the brains of the eight patients who had volunteer ed for the study.

The human clinical trial was undertaken following extensive studies in primates conducted by Tuszynski and colleagues, which showed that grafting NGF-producing tissue into the brains of aged monkeys restored atrophied brain cells to near-normal size and quantity, and also restored axons connecting the brain cells, essential for communication between cells. The recent human studies were a Phase I clinical trial, designed to test safety and toxicity. The procedure was initially performed while patients were awake but lightly sedated, and two patients moved as the cells were being injected, resulting in bleeding in the brain. One of these patients died five week later. As a result of the bleeds, the protocol was redesigned to perform the procedure under general anesthesia and all subsequent procedures were performed without complication.

Cognitive outcomes were assessed in the six patients who completed the NGF delivery procedure safely. The Mini Mental Status Examination (MMSE), which evaluates cognitive function, was administered at screening, the time of treatment and at several intervals after treatment. Over an average post-treatment follow-up period of 22 months, the rate of decline on the MMSE among NGF-treated patients was reduced by as much as 51 percent. An additional test, called the Alzheimer's Disease Assessment Scale-Cognitive Subcomponent, or ADAS-Cog, also showed improvements in rates of decline followed the MMSE findings.

Post-operative PET scans in four subjects showed significant increases in the brain's absorption of a radioisotope called 18-fluorodeoxyglucose, an indicator of increased metabolic activity in the brain. The researchers noted that the increase was observed in most cortical regions that receive cholinergic input from forebrain nerve cells called the nucleus basalis, and in the cerebellum, a structure associated with cortical plasticity.

In addition to Tuszynski, authors of the paper in Nature Medicine, were Leon Thal, M.D., UCSD chair of neurosciences, director of the UCSD Shiley-Marcos Alzheimer's Disease Research Center (ADRC), and a neurologist with the VA San Diego Healthcare System; Mary Margaret Pay., R.N., David P. Salmon, Ph.D., Armin Blesch, Ph.D., Gilbert Ho, M.D., Gang Tong, M.D., Lawrence Hansen, M.D., and James Conner, Ph.D., of the UCSD Department of Neurosciences; Hoi Sang U, M.D., UCSD Department of Surgery; Lee Vahlsing, M.S., UCSD Department of Neurosciences and VA San Diego Healthcare System; Roy Bakay, M.D., Rush University Department of Surgery; Piyush Patel, M.D., UCSD Department of Anesthesiology; Steven G. Potkin, M.D. and Christine Gall, Ph.D., UC Irvine Department of Neurology; James Fallon, Ph.D., UC Irvine Department of Neurobiology; Elliott J. Mufson, Ph.D. and Jeffrey H. Kordower, Ph.D., Rush University Department of Neurosciences.


Source:University of California - San Diego

Related biology news :

1. Neuronal traffic jam marks early Alzheimers disease
2. Mouse brain cells rapidly recover after Alzheimers plaques are cleared
3. Gene vaccine for Alzheimers disease shows promising results
4. Duke Chemists Isolating Individual Molecules Of Toxic Protein In Alzheimers, Parkinsons Disease
5. Nanoscale Diagnostic Sets Sights on Alzheimers
6. One gene links newborn neurons with those that die in diseases such as Alzheimers
7. Scientists discover that three molecules may be developed into new Alzheimers drugs
8. Pinpointing a culprit molecule in Alzheimers disease
9. Targeting a key enzyme with gene therapy reversed course of Alzheimers disease in mouse models
10. Hope for Alzheimers blossoms
11. Natural compound from pond scum shows potential activity against Alzheimers
Post Your Comments:

(Date:11/12/2015)... CAMBRIDGE, Mass. , Nov. 12, 2015 /PRNewswire/ ... Broad Institute of MIT and Harvard for use ... chemical discovery information management tools. The partnership will ... share both biological and chemical research information internally ... tools will be used for managing the Institute,s ...
(Date:11/9/2015)... 09, 2015 ... the "Global Law Enforcement Biometrics Market ... --> ) has announced the ... Biometrics Market 2015-2019" report to their ... ( ) has announced the addition ...
(Date:10/29/2015)... Calif. , Oct. 29, 2015  The J. ... new report titled, "DNA Synthesis and Biosecurity: Lessons Learned ... the Department of Health and Human Services guidance for ... in 2010. --> ... it also has the potential to pose unique biosecurity ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... 24, 2015 , ... The United States Golf Association (USGA) today announced Dr. ... Award. Presented annually since 1961, the USGA Green Section Award recognizes an individual’s distinguished ... , Clarke, of Iselin, N.J., is an extension specialist of turfgrass pathology in ...
(Date:11/24/2015)... ... November 24, 2015 , ... International Society for Pharmaceutical ... the premier annual events for pharmaceutical manufacturing: 2015 Annual Meeting. The conference took ... hosted the largest number of attendees in more than a decade. , ...
(Date:11/24/2015)... , ... November 24, 2015 , ... The Academy of ... Interest Group (SIG), MultiGP, also known as Multirotor Grand Prix, to represent the First–Person ... few years. Many AMA members have embraced this type of racing and several new ...
(Date:11/24/2015)... FRANCISCO , Nov. 24, 2015  Twist ... announced that Emily Leproust, Ph.D., Twist Bioscience chief ... Jaffray Healthcare Conference on December 1, 2015 at ... Hotel in New York City. --> ... . Twist Bioscience is on Twitter. ...
Breaking Biology Technology: