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Safe drug touted as able to cure “Rain Man”-like mice

Dec. 9, 2010
Courtesy of Eastern Virginia Medical School
and World Science staff

Re­search­ers have an­nounced a pos­si­bly ma­jor ad­vance in treat­ing au­tism spec­trum dis­or­ders, whose vic­tims face an of­ten crip­pling in­abil­ity to in­ter­act so­cially, some­times ac­com­pa­nied by un­usu­al tal­ents.

A strain of mice with an au­tism-like con­di­tion showed a re­ver­sal of the symp­toms thanks to a drug al­ready shown to be safe in hu­mans, sci­en­tists say.

Au­tism spec­trum dis­or­ders were fa­mously por­trayed in the 1988 film “Rain Man.” Ac­tor Dus­tin Hoff­man’s char­ac­ter dis­plays an ex­treme case of au­tism along with seem­ingly su­per­hu­man mem­o­ry and count­ing skills, which his broth­er seeks to turn to fi­nan­cial ad­van­tage at the gam­ing ta­bles.

But se­verely af­fect­ed au­tism spec­trum pa­tients ex­pe­ri­ence an­y­thing but a life of silver-screen glam­or. “Per­sons with Au­tism Spec­trum Dis­or­ders are ei­ther dis­in­ter­est­ed in so­cial in­ter­actions or find them un­pleas­ant. They of­ten don’t un­der­stand what oth­er peo­ple are think­ing or feel­ing and mis­in­ter­pret so­cial cues,” said Ste­phen I. Deutsch, psy­chi­a­trist at East­ern Vir­gin­ia Med­i­cal School in Nor­folk, Va. That, he added, prompts a cas­cade of un­for­tu­nate reper­cus­sions.

“You might have some­one with a 125 or 130 I.Q. who’s un­em­ploy­able” be­cause of their so­cial im­pair­ments, said psy­chi­a­trist Ma­ria R. Ur­bano, al­so of the school.

“Sadly, per­sons with au­tism spec­trum dis­or­ders are of­ten pain­fully aware of their lim­it­ed so­cia­bil­ity, which can lead to pro­found feel­ings of sad­ness and frustra­t­ion,” Deutsch added.  As many as 1.5 mil­lion Amer­i­cans have some form of au­tism, ac­cord­ing to the Be­thes­da, Md.-based Au­tism So­ci­e­ty of Amer­i­ca.

Ad­di­tion­al com­mon symp­toms of au­tism spec­trum dis­or­ders in­clude an ab­nor­mal at­tach­ment to rou­tine, fre­quent lack of emo­tion­al ex­pres­sive­ness, and in­ter­ests that be­come ob­ses­sive, ac­cord­ing to the U.S. Na­tional In­sti­tute of Men­tal Health. But com­plic­at­ing the pic­ture, the dis­orders are some­times as­soc­iated with per­sonal qual­i­ties that pa­tients and their ad­vo­cates may see as posi­tive and worth fost­er­ing—for in­stance, a re­fresh­ing non­con­form­ity or dis­int­er­est in super­fi­cial chat­ter.

In the new stu­dy, Deutsch, Urbano and col­leagues didn’t delve into such questions, but did ver­i­fy, they said, that a mouse strain known as BAL­B/c is a val­id an­i­mal mod­el of the lim­it­ed so­cia­bil­ity seen in per­sons with au­tism spec­trum dis­or­ders. In the pres­ence of anoth­er mouse, the af­fect­ed mice move as far away as pos­si­ble and don’t in­ter­act as nor­mal mice do.

The in­ves­ti­ga­tors tested wheth­er ad­min­is­ter­ing a par­tic­u­lar drug might change the pic­ture by al­ter­ing the func­tion of cer­tain re­cep­tors in the brain. Re­cep­tors are com­plexes of mo­le­cules that serve as gate­ways through which oth­er mo­le­cules can de­liv­er sig­nals in­to cells. 

The med­ica­t­ion used, D-Cycloserine, orig­i­nally was de­vel­oped to treat tu­ber­cu­losis, but pre­vi­ous stud­ies showed, by chance, that it might change so­cial be­hav­ior. In pre­lim­i­nar­y stud­ies at the med­ical school, the med­ica­t­ion seemed to re­solve the Bal­b/c mouse’s deficits of so­cia­bil­ity; it be­haved as a nor­mal mouse would when placed near anoth­er, re­search­ers re­ported.

Deutsch is scheduled to give a talk on the findings Dec. 14 at the med­ical school’s quar­terly Au­tism Educa­t­ion Se­ries. Ur­bano plans to start a pi­lot clin­i­cal tri­al of D-Cy­clo­ser­ine in ad­o­les­cent and young adult pa­tients with au­tism spec­trum dis­or­ders. The tri­al is de­signed show wheth­er the med­ica­t­ion, al­ready dem­on­strat­ed safe for use in hu­mans, works as well in our spe­cies as it does on mice, Ur­ba­no said.

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Researchers have announced a possible “breakthrough” in treating autism spectrum disorders, whose victims face an often crippling inability to interact socially, sometimes accompanied by unusual talents. Mice genetically engineered to exhibit an autism-like condition showed a reversal of the symptoms thanks to a drug already shown to be safe in humans, scientists say. Autism spectrum disorders were famously portrayed in the movie 1988 film “Rain Man.” Actor Dustin Hoffman’s character displays an extreme case of autism along with seemingly superhuman memory and counting skills, which his brother seeks to turn to financial advantage at the gaming tables. But those severely affected autism spectrum patients experience anything but a life of silver-screen glamor. “Persons with Autism Spectrum Disorders are either disinterested in social interactions or find them unpleasant. They often don’t understand what other people are thinking or feeling and misinterpret social cues,” said Stephen I. Deutsch, psychiatrist at Eastern Virginia Medical School in Norfolk, Va. That, he added, prompts a cascade of unfortunate repercussions. “You might have someone with a 125 or 130 I.Q. who’s unemployable” because of their social impairments, said psychiatrist Maria R. Urbano, also of the school. “Sadly, persons with autism spectrum disorders are often painfully aware of their limited sociability, which can lead to profound feelings of sadness and frustration,” Deutsch added. Additional common symptoms of autism spectrum disorders include an abnormal attachment to routine, frequent lack of emotional expressiveness, and interests that become obsessive, according to the U.S. National Institute of Mental Health. In the study, scientists at the institution said they verified that a mouse strain known as the BALB/c mouse is a valid animal model of the limited sociability seen in persons with autism spectrum disorders. In the presence of another mouse, the affected mice move as far away as possible and don’t interact as normal mice do. The investigators tested whether administering a particular drug might change the picture by altering the function of certain receptors in the brain. Receptors are complexes of molecules that serve as gateways through which other molecules can deliver signals into cells. The medication used, D-Cycloserine, originally was developed to treat tuberculosis, but previous studies showed, by chance, that it might change social behavior. In preliminary studies at the medical school, the medication seemed to resolve the Balb/c mouse’s deficits of sociability; it behaved as a normal mouse would when placed near another, researchers reported. Deutsch plans to give a talk on the research Dec. 14 at the medical school’s quarterly Autism Education Series. Urbano plans to start a pilot clinical trial of D-Cycloserine in adolescent and young adult patients with autism spectrum disorders. The trial is designed show whether the medication, already demonstrated safe for use in humans, works as well in our species as it does on mice, Urbano said. As many as 1.5 million Americans have some form of autism, according to the Bethesda, Md.-based Autism Society of America.