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Diabetes Drugs Could be Used as Brain Injury Treatments
Metformin is a widely used diabetes drug, particularly used to treat type-2 diabetes. However, recent experiments indicate that it could also offer benefits to those with nervous system damage.
Though no tests have been conducted on humans yet, a series of experiments, first in cultures and then on mice, indicate that the drug promotes the growth of new neurons. In a classic behavioral test, mice that had been treated with metformin were able to form new memories faster than those mice who had been treated with a control substance.
Freda Miller, PhD, of the Hospital for Sick Children in Toronto and her colleagues, who conducted the metformin experiments, revealed that metformin could be an important aid to stem cell therapies by activating the aPKC—CBP pathway in neural stem cells, thus creating new neurons. Experiments in culture have been quite promising, showing that metformin promotes neurogenesis in human neural stem cells. In living mice, a 12-day treatment of metformin increased the number of new neurons by about 30%.
Interestingly enough, Chaim Pick of Tel Aviv University’s Sackier Faculty of Medicine and the Us National Institute of Aging’s Dr. Nigel Grieg have discovered that another FDA-approved diabetes drug, Exendin-4, significantly minimizes TBI animal models when administered after an accident.
To test the hypothesis, anesthetized mice were exposed to controlled explosions 8-11 meters away and their resulting injuries were then analyzed. Mice treated with Exendin-4 showed brain function nearly on par with the control group, while the group of mice who were exposed to the blast without being treated with Exendin-4 showed more severe brain injuries.
According to Chaim Pick, “Now we need to find the right dosage and delivery system, then build a cocktail of drugs that will increase the therapeutic value of this concept.”
Chaim Pick has worked with the U.S. military, conducting research to minimize the damage of soldiers exposed to the types of blasts that could be caused by IUDs or terrorist attacks. Exendin-4 could be used in the not-too-distant future as a brain injury treatment for U.S. soldiers.
While the possible breakthroughs offered by these diabetes drugs have yet to help human patients with brain injuries, they offer hope that new treatments are around the corner.
I work on many TBI cases and the most common form of treatment initially seems to be re-learning what was lost in the injury. However, many people do not even suffer the effects of the damage for decades and have no idea what is happening. I stay current on the research and wonder why US hospitals and medical research centers are not as progressive as Europe or Israel. Its’ bothersome that the symptoms are treated as they come and there is not more available to the average patient in terms of hope for repair on the medical horizon.
My website is quite out of date but more recent reviews are listed below. In our laboratory work we found that drugs increasing NA in the CNS can promote recovery after stroke but were not effective after TBI. But for both stroke & TBI, I can say “Do no harm” by administering drugs reducing NA & commonly prescribed for agitation in TBI or stroke patients. The most relevant articles are.cited in these reviews:
REVIEWS
Most cited:
DIASCHISIS FEENEY, DM & BARON, JC STROKE Vol. 17 Issue: 5 Pgs.:817-830 1986
Other reviews:
Noradrenergic modulation of hemiplegia: Facilitation and maintenance of recovery
Feeney, DM (Feeney, De Smet, AM; Rai, RESTORATIVE NEUROLOGY AND NEUROSCIENCE Volume: 22 Issue: 3-5 Pages: 175-190, 2004
PHARMACOTHERAPY FOR RECOVERY OF FUNCTION AFTER BRAIN INJURY
FEENEY, DM & SUTTON, RL CRITICAL REVIEWS IN NEUROBIOLOGY Vol. 3 Issue: 2 Pigs. 135-197,: 1987
Norepinephrine and brain damage: Alpha noradrenergic pharmacology alters functional recovery after cortical trauma. Feeney, D.M.& Westerberg, V. S. Canadian Journal of Psychology, 1990, 44, 233-252. (Invited article for a special issue on Recovery of Function and Neuroplasticity).
I hope these may be of interest to you, TBI is a difficult problem.
Dennis M. Feeney
Prof. Emeritus
Neurosciences, The University of New Mexico