Cancer Drug Shows Promise For Inherited Form Of Dementia


Frontotemporal dementia characterized by degeneration of the frontal lobe: image via ask.comFrontotemporal dementia characterized by degeneration of the frontal lobe: image via Scientists from the Center for Alzheimer’s and Neurodegenerative Diseases at the University of Texas (UT) Southwestern Medical Center have discovered that the drug SAHA (suberoylanilide hydroxamic acid) shows promise as a potential therapy for familial frontotemporal dementia (FTD).  As yet, there is no treatment for the neurological disease, the second most common non-elderly dementia.

FTD is usually diagnosed around the age of 60 though its symptoms may appear much earlier. Its onset is followed by a decline in decision-making ability, behavioral control, and/or language skills. About 25 percent of FTD patients have the familial or inherited form of the disease, in which one copy of the granulin (GRN) gene is normal and one is mutated, thus limiting the reproduction of GRN - a gene that is essential for the survival of nerve cells.

In studies performed by members of the UT Center, UCLA, UCSF, and the University of Massachusetts Medical School, SAHA effectively increased the GRN levels in cultured mouse cells and restored near-normal GRN levels in cells from human subjects with FTD. 

“We found a drug that can overcome the chemical deficiency associated with the condition, and we showed that it worked in cells taken from humans with FTD,” co-senior author of the study Dr. Gang Yu said.

The group will continue studying the effects of other chemicals to find additional GRN-stimulating drugs for human trials, as it is not yet known whether SAHA will be able to cross the blood-brain barrier, a biologically protective system that keeps many chemicals from reaching the brain.  

But human trials will be attempted, hopefully quickly.  Dr. Joachim Herz, author of the study and director of the UT Center, said it was hoped that because SAHA is already approved for clinical use, it  "should make it easer to move quickly to human trials."

SAHA has been approved for treatment of a cancer called cutaneous T-cell lymphoma.


Sources: UTSouthwestern, Genetics Home Reference The study appears in the May 27th issue of The Journal of Biological Chemistry