Friday, March 25, 2011

Making Replacement Brain Cells Research in Progress


Last night, I went to a lecture at the University of Texas Southwestern Medical Center, a National Institute of Health research site. It was on the work of Dr. Steven McKnight and Dr. Andrew Pieper.

Carole B. Larkin
By Carole B. Larkin
Alzheimer's Reading Room

This is early stage research. The hope is that they can move steadily forward and discover a treatment that works with humans.

Imagine growing new brain cells to replace the ones that die! Wow!!! Now, that’s hope!

Here is some previously released information on the research of Steven McKnight and Andrew Pieper.


Mental decline thwarted in aging rats

Scientists have discovered a compound that restores the capacity to form new memories in aging rats, likely by improving the survival of newborn neurons in the brain's memory hub. The research, funded in part by the National Institutes of Health, has turned up clues to a neuroprotective mechanism that could lead to a treatment for Alzheimer's disease.

"This neuroprotective compound, called P7C3, holds special promise because of its medication-friendly properties," explained Steven McKnight, Ph.D., who co-led the research with Andrew Pieper, M.D., Ph.D., both of University of Texas Southwestern Medical Center, Dallas. "It can be taken orally, crosses the blood-brain barrier with long-lasting effects, and is safely tolerated by mice during many stages of development."

The researchers report on their findings July 9, 2010 in the journal Cell. Their work was funded, in part, by the NIH's National Institute of Mental Health (NIMH), a NIH Director's Pioneer Award funded through the Common Fund and managed by the National Institute of General Medical Sciences, and National Cancer Institute.

"This striking demonstration of a treatment that stems age-related cognitive decline in living animals points the way to potential development of the first cures that will address the core illness process in Alzheimer's disease," said NIMH Director Thomas Insel, M.D.

Physical activity, social, or other enriching experiences promote neurogenesis – the birth and maturation of new neurons. This growth takes place in the dentate gyrus, a key area of the brain's memory hub, the hippocampus. But even in the normal adult brain, most of these newborn neurons die during the month it takes to develop and get wired into brain circuitry. To survive, the cells must run a gauntlet of challenges. Newborn hippocampus neurons fare much worse in aging-related disorders like Alzheimer's, marked by runaway cell death.

In hopes of finding compounds that might protect such vulnerable neurons during this process, Pieper, McKnight and colleagues tested more than 1000 small molecules in living mice. One of the compounds, designated P7C3, corrected deficits in the brains of adult mice engineered to lack a gene required for the survival of newborn neurons in the hippocampus. Giving P7C3 to the mice reduced programmed death of newborn cells – normalizing stunted growth of branch-like neuronal extensions and thickening an abnormally thin layer of cells by 40 percent. Among clues to the mechanism by which P7C3 works, the researchers discovered that it protects the integrity of machinery for maintaining a cell's energy level.

To find out if P7C3 could similarly stem aging-associated neuronal death and cognitive decline, the researchers gave the compound to aged rats. Rodents treated with P7C3 for two months significantly outperformed their placebo-treated peers on a water maze task, a standard assay of hippocampus-dependent learning. This was traced to a threefold higher-than-normal level of newborn neurons in the dentate gyrus of the treated animals. Rats were used instead of mice for this phase of the study because the genetically engineered mice could not swim.

The researchers pinpointed a derivative of P7C3, called A20, which is even more protective than the parent compound. They also produced evidence suggesting that two other neuroprotective compounds eyed as possible Alzheimer's cures may work through the same mechanism as P7C3. The A20 derivative proved 300 times more potent than one of these compounds currently in clinical trials for Alzheimer's disease. This suggested that even more potent neuroprotective agents could potentially be discovered using the same methods. Following up on these leads, the researchers are now searching for the molecular target of P7C3 – key to discovering the underlying neuroprotective mechanism.

Reference:

Discovery of a Pro-neurogenic, Neuroprotective Chemical. Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM, Becker GL, Huntington P, Goldman SE, Shen CH, Capota M, Britt JK, Kotti T, Ure K, Brat DJ, Williams NS, MacMillan KS, Naidoo J, Melito L, Hsieh J, Brabander JD, Ready JM, McKnight SL. 2010, Jul 8. Cell

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit www.nimh.nih.gov.

The NIH Common Fund encourages collaboration and supports a series of exceptionally high impact, trans-NIH programs. These new programs are funded through the Common Fund, and managed by the NIH Office of the Director in partnership with the various NIH Institutes, Centers and Offices. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Common Fund can be found at http://commonfund.nih.gov.

NIGMS is a part of NIH that supports basic research to increase our understanding of life processes and lay the foundation for advances in disease diagnosis, treatment and prevention. For more information on the Institute's research and training programs, see http://www.nigms.nih.gov.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.



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Carole Larkin MA,CMC,CAEd,QDCS,EICS,
is a Geriatric Care Manager who specializes in helping families with Alzheimer’s and related dementias issues. She also trains caregivers in home care companies, assisted livings, memory care communities, and nursing homes in dementia specific techniques for best care of dementia sufferers. ThirdAge Services LLC, is located in Dallas, TX.


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Original content Bob DeMarco, the Alzheimer's Reading Room