Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study explores gene transfer to modify underlying course of Alzheimer’s disease

21.09.2004


New technique that uses gene therapy delivers nerve growth factor into regions of the brain where neurons are degenerating, in order to prevent cell death and reverse cell atrophy.

Investigators at Rush University Medical Center have successfully initiated a new technique that uses gene therapy to deliver nerve growth factor into regions of the brain where neurons are degenerating, in order to prevent cell death and reverse cell atrophy, two hallmarks of Alzheimer’s disease. If successful, this could be a major step toward modifying the course of the disease. Rush is the only center in this study.

The new technique uses CERE-110 as the gene therapy agent. CERE-110 carries the Nerve Growth Factor (NGF) gene encased in a harmless viral coating, which protects the gene and facilitates its delivery to brain cells. The active part of the drug is the NGF gene, the human DNA strand that codes for the NGF protein, a natural substance that exerts positive effects on brain cells. A key objective of the study is to deliver the CERE-110 directly to the part of the brain that is almost universally affected by Alzheimer’s disease, the basal forebrain, and not to other parts of the brain where it may cause side effects.



The new drug, CERE-110, is being used by researchers at Rush as part of a Phase I study to evaluate its safety and tolerability using two different doses. Memory and cognitive function will also be assessed regularly during the two-year period of the study. Six to 12 subjects with mild to moderate Alzheimer’s disease, based on the specific cognitive tests used to classify the disease stage, will be enrolled in the study.

The first patient in the study was treated on July 27. Dr. David Bennett and Dr. Zoe Arvanitakis of the Rush Alzheimer’s Disease Center are the co-principal investigators. Bennett is director of the center. Ceregene, Inc., based in San Diego, (a minority owned subsidiary of Cell Genesys, Inc.) the developer and manufacturer of CERE-110, is funding the study.

Neurosurgery is required to precisely inject the drug into the nucleus basalis of Meynert on both sides of the brain. Dr. Roy Bakay, a Rush neurosurgeon and member of the Chicago Institute of Neurosurgery and Neuroresearch medical group, performs the surgery. Bakay is experienced in stereotactic injection and performed some of the surgeries for an earlier study at the University of California, San Diego. While neurosurgery is used to deliver NGF in both studies, the precise method of drug delivery in the Rush study has been modified in order to decrease risk and increase the potential benefit of NGF.

Results from a Phase I study by Dr. Mark Tuszynski at the University of California, San Diego, determined that there were no adverse effects from NGF detected in the subjects, an indication that the biological therapy is itself safe and well tolerated. Since the study was small and did not include placebo controls, apparent trends toward improvements in rate of cognitive decline and brain activity noted by Dr. Tuszynski must be interpreted with extreme caution. This study used genetically modified skin cells to deliver the NGF. Results from that study were presented at the American Academy of Neurology meeting in Philadelphia this past April. The study being conducted at Rush uses a more sophisticated means of delivering NGF to the brain and does not require a skin biopsy or the use of skin cells.

Alzheimer’s disease is caused by brain degeneration and is marked by the death of cells, particularly the cells (cholinergic neurons) in the basal forebrain. These cells are the primary source of the brain chemical messenger (neurotransmitter) called acetylcholine. Alzheimer’s disease impairs the production of acetylcholine, one of the main chemical messengers in the brain that is important for memory and cognitive function.

"If you can positively affect the basal forebrain, it may have a widespread effect on the entire brain because projections from that area reach out to all other parts of the brain, delivering the important neurotransmitter acetylcholine," said Arvanitakis.

Until recently, there was no practical method to deliver NGF to the specific areas of the brain where neurons were degenerating in Alzheimer’s disease. Indiscriminate delivery of NGF to the brain would cause side effects, such as weight loss and pain.

The virus coating (AAV vector) that carries the NGF gene is well studied and has been used in several other gene transfer studies to deliver different genes to treat cancer, cystic fibrosis, and Parkinson’s disease. "Until now, it has not been used in Alzheimer’s disease," Arvanitakis said. "The vector is no longer a true virus as it cannot replicate on its own and must be in the presence of another virus to be active. The vector will transfer the gene for NGF only to the area of the brain where it is placed. The virus is common; most people have already been exposed to it and so have developed antibodies to the virus in their blood," she explained.

Currently, there are five Food and Drug Administration (FDA) approved medications for use in treating cognitive symptoms in patients with Alzheimer’s disease. Four try to boost the brain levels of acetylcholine by blocking the enzyme that breaks down acetylcholine. The fifth drug acts on another brain chemical. None of the available drugs are known to change the underlying neurobiology of the disease.

Extensive studies in several animal models, including primates, showed that NGF or NFG gene delivery to the basal forebrain prevented the death of the same group of cells (cholinergic neurons) which undergo severe degeneration and death in Alzheimer’s disease patients. NGF restored atrophied (shrunken) brain cells to near-normal size and quantity and also restored axons connecting the brain cells, essential for communication between cells. In humans, loss of cholinergic cells correlates with dementia severity, the density of amyloid plaques (which are abnormal protein deposits in the brains of patients with Alzheimer’s disease), and loss of synapses in the brains of Alzheimer’s disease patients.

Alzheimer’s disease is a common disease in aging, currently affecting approximately 4.5 million Americans. The number will increase as the older segment of the population increases. If there are no significant improvements in treatment, there will be a three-fold increase in the number of persons with Alzheimer’s disease in the U.S. by 2050.

John Pontarelli | EurekAlert!
Further information:
http://www.rush.edu

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>