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:
*Name:
*Comment:
*Email:


(Date:6/3/2016)... June 3, 2016 ... Nepal hat ein ... hochsicherer geprägter Kennzeichen, einschließlich Personalisierung, Registrierung und ... der Produktion und Implementierung von Identitätsmanagementlösungen. Zahlreiche ... im Januar teilgenommen, aber Decatur wurde als ...
(Date:6/2/2016)... NEW YORK , June 2, 2016   The ... (Weather), is announcing Watson Ads, an industry-first capability in which ... advertising, by being able to ask questions via voice or ... Marketers have long ... with the consumer, that can be personal, relevant and valuable; ...
(Date:6/1/2016)... YORK , June 1, 2016 ... Technology in Election Administration and Criminal Identification to Boost ... to a recently released TechSci Research report, " Global ... By Region, Competition Forecast and Opportunities, 2011 - 2021", ... 24.8 billion by 2021, on account of growing security ...
Breaking Biology News(10 mins):
(Date:6/27/2016)...  Sequenom, Inc. (NASDAQ: SQNM ), a ... the development of innovative products and services, announced today ... States denied its petition to review decisions ... U.S. Patent No. 6,258,540 (",540 Patent") are not patent ... Supreme Court,s Mayo Collaborative Services v. Prometheus Laboratories decision.  ...
(Date:6/27/2016)... PHILADELPHIA , June 27, 2016  Liquid ... today announced the funding of a Sponsored Research ... study circulating tumor cells (CTCs) from cancer patients.  ... changes in CTC levels correlate with clinical outcomes ... therapies. These data will then be employed to ...
(Date:6/24/2016)... ... ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical journal articles ... findings are the subject of a new article on the Surviving Mesothelioma website. ... blood, lung fluid or tissue of mesothelioma patients that can help point doctors to ...
(Date:6/23/2016)... 2016 A person commits a crime, and the ... track the criminal down. An outbreak of foodborne ... Administration (FDA) uses DNA evidence to track down the bacteria ... far-fetched? It,s not. The FDA has increasingly used a complex, ... foodborne illnesses. Put as simply as possible, whole genome sequencing ...
Breaking Biology Technology: