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Stem cells found to cure epilepsy in mice

May 6, 2013
Courtesy of UCSF
and World Science staff

Bi­ol­o­gists re­port that they have cured seizures in ep­i­lep­tic mice us­ing a one-time trans­planta­t­ion of stem cells that in­hib­it sig­nal­ing in over­ac­tive nerve cir­cuits.

The re­search­ers put the em­bry­on­ic stem cells, or pro­gen­i­tor cells, in­to the hip­po­cam­pus, a brain re­gion as­so­ci­at­ed with seizures, as well as learn­ing and mem­o­ry. Oth­er re­search­ers had pre­vi­ously used dif­fer­ent cell types in ro­dent cell trans­planta­t­ion ex­pe­ri­ments and failed to stop seizures, ac­cord­ing to the sci­en­tists.

Cur­rent ep­i­lep­sy med­ica­t­ions only con­trol symp­toms and not the causes, said Scott C. Bara­ban, a neu­ro­sci­ent­ist at the Uni­vers­ity of Cal­i­for­nia San Fran­cis­co who led the new stu­dy. In many types of ep­i­lep­sy, he added, the drugs don’t even work.

“This pro­ce­dure of­fers the pos­si­bil­ity of con­trolling seizures and res­cu­ing cog­ni­tive deficits in these pa­tients,” al­though more re­search is needed, he said. “This is the first re­port in a mouse mod­el of adult ep­i­lep­sy in which mice that al­ready were hav­ing seizures stopped hav­ing seizures af­ter treat­ment.” The find­ings were pub­lished on­line May 5 in the jour­nal Na­ture Neu­ro­sci­ence.

Dur­ing ep­i­lep­tic seizures, ex­treme mus­cle con­trac­tions and, of­ten, loss of con­scious­ness can lead pa­tients to lose con­trol, fall and some­times suf­fer se­ri­ous in­ju­ry. The cause is the ab­nor­mal fir­ing of many ex­cit­a­to­ry nerve cells in the brain at the same time. The trans­planted cells, called me­di­al gan­gli­on­ic em­i­nence cells, quenched this fire­storm, end­ing seizures in half of the treated mice and dra­mat­ic­ally re­duc­ing the num­ber of spon­ta­ne­ous seizures in the rest, ac­cord­ing to the sci­en­tists.

They al­so re­ported May 2 in the jour­nal Cell Stem Cell that they found a way to re­liably gen­er­ate si­m­i­lar cells, but hu­man ver­sions, in the lab­o­r­a­to­ry.

In many forms of ep­i­lep­sy, loss or mal­func­tion of in­hib­ito­ry nerve cells with­in the hip­po­cam­pus plays a crit­i­cal role. The trans­planted cells in ques­tion are pro­gen­i­tor cells that form early with­in the em­bry­o and are ca­pa­ble of gen­er­at­ing ma­ture in­hib­ito­ry nerve cells called in­terneu­rons. In the new stu­dy, the trans­planted cells from mouse em­bry­os mi­grat­ed and gen­er­ated in­terneu­rons, in ef­fect re­plac­ing the cells that fail in ep­i­lep­sy, the sci­en­tists ex­plained. The new cells in­te­grat­ed in­to ex­ist­ing neu­ral cir­cuits in the mice, the re­search­ers found.

“These cells mi­grate widely and in­te­grate in­to the adult brain as new in­hib­ito­ry neu­rons,” Bara­ban said. 

The mouse mod­el of dis­ease that Bara­ban's lab team worked with is meant to re­sem­ble a se­vere and typ­ic­ally drug-resistant form of hu­man ep­i­lep­sy called me­si­al tem­po­ral lobe ep­i­lep­sy, in which seizures are thought to arise in the hip­po­cam­pus.

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Biologists report that they have cured seizures in epileptic mice using a one-time transplantation of stem cells that inhibit signaling in overactive nerve circuits. The researchers put the embryonic stem cells, or progenitor cells, into the hippocampus, a brain region associated with seizures, as well as learning and memory. Other researchers had previously used different cell types in rodent cell transplantation experiments and failed to stop seizures, according to the scientists. Current epilepsy medications only control symptoms and not the causes, said Scott C. Baraban, a neuroscientist at the University of California San Francisco who led the new study. In many types of epilepsy, he added, the drugs don’t even work. “This procedure offers the possibility of controlling seizures and rescuing cognitive deficits in these patients,” he said. “This is the first report in a mouse model of adult epilepsy in which mice that already were having seizures stopped having seizures after treatment.” The findings were published online May 5 in the journal Nature Neuroscience. During epileptic seizures, extreme muscle contractions and, often, loss of consciousness can lead patients to lose control, fall and sometimes suffer serious injury. The cause is the abnormal firing of many excitatory nerve cells in the brain at the same time. The transplanted cells, called medial ganglionic eminence cells, quenched this firestorm, ending seizures in half of the treated mice and dramatically reducing the number of spontaneous seizures in the rest, according to the scientists. They also reported May 2 in the journal Cell Stem Cell that they found a way to reliably generate similar cells, but human versions, in the laboratory. In many forms of epilepsy, loss or malfunction of inhibitory nerve cells within the hippocampus plays a critical role. The transplanted cells in question are progenitor cells that form early within the embryo and are capable of generating mature inhibitory nerve cells called interneurons. In the new study, the transplanted cells from mouse embryos migrated and generated interneurons, in effect replacing the cells that fail in epilepsy, the scientists explained. The new cells integrated into existing neural circuits in the mice, the researchers found. “These cells migrate widely and integrate into the adult brain as new inhibitory neurons,” Baraban said. The mouse model of disease that Baraban's lab team worked with is meant to resemble a severe and typically drug-resistant form of human epilepsy called mesial temporal lobe epilepsy, in which seizures are thought to arise in the hippocampus.