Kristina Chew, PhD on June 23rd, 2008 – AutismVox
A letter abstract in the June 22nd Nature Medicine is entitled Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis. Tuberous sclerosis is a rare genetic disease that affects the central nervous system and causes benign tumors to grow on the brain, kidneys, heart, eyes, lungs, and skin. Those with TSC can also have seizures, mental retardation, behavior problems, and skin abnormalities as well as developmental delays and autism: In fact, half of those with TSC have autism and epilepsy. Mutations in one of two genes, TSC1 and TSC2, been have identified as causes of TSC. The Nature Medicine abstract also notes that “even individuals with tuberous sclerosis and a normal intelligence quotient (approximately 50%) are commonly affected with specific neuropsychological problems, including long-term and working memory deficits.”

In the study, which was carried out by researchers from UCLA, mice were bred to have TSC; they specifically had deficits in learning and memory. By giving the mice rapamycin, a drug that has been approved by the FDA to fight tissue rejection following organ transplants, their learning and memory deficits were reversed. From a press release containing interviews with the study’s researchers:

Rapamycin is well-known for targeting an enzyme involved in making proteins needed for memory. The UCLA team chose it because the same enzyme is also regulated by TSC proteins.

“This is the first study to demonstrate that the drug rapamycin can repair learning deficits related to a genetic mutation that causes autism in humans. The same mutation in animals produces learning disorders, which we were able to eliminate in adult mice,” explained principal investigator Dr. Alcino Silva, professor of neurobiology and psychiatry at the David Geffen School of Medicine at UCLA. “Our work and other recent studies suggest that some forms of mental retardation can be reversed, even in the adult brain.”

“These findings challenge the theory that abnormal brain development is to blame for mental impairment in tuberous sclerosis,” added first author Dan Ehninger, postgraduate researcher in neurobiology. “Our research shows that the disease’s learning problems are caused by reversible changes in brain function — not by permanent damage to the developing brain.”

………

“Memory is as much about discarding trivial details as it is about storing useful information,” said Silva, a member of the UCLA Department of Psychology and UCLA Brain Research Institute. “Our findings suggest that mice with the mutation cannot distinguish between important and unimportant data. We suspect that their brains are filled with meaningless noise that interferes with learning.”

“After only three days of treatment, the TSC mice learned as quickly as the healthy mice,” said Ehninger. “The rapamycin corrected the biochemistry, reversed the learning deficits and restored normal hippocampal function, allowing the mice’s brains to store memories properly.”

Regan commented about the study on an earlier post; the researchers’ association of intelligence with learning and memory is particularly interesting to me, and also Dr. Silva’s definition of memory as being “‘as much about discarding trivial details as it is about storing useful information.’” My son Charlie has a great and powerful memory: He never seems to forget a therapist or teacher, a place we’ve been and the route to it, a toy or food or activity that he’s liked a lot. He tends to get stuck—fixate—on those first, earlier things he’s learned and to have trouble learning new things (getting used to new teachers and therapists, going to new places along new routes, playing with new toys and trying new foods and activities). Often it seems that the first of many things is what “something is” for Charlie and teaching him otherwise evokes cognitive dissonance,” as if he’s pushing against something in his brain to accommodate for something new.

I’ve noted Charlie’s longstanding struggles to learn the alphabet and language (both understanding and speaking it). Regarding the alphabet: We started to teach it to him when he was about 3 1/2; he’d had no trouble learning numbers. It has taken years for Charlie to recognize the letters and sometimes he seems to be focusing on certain details of the letters—certain shapes and the fact that to many letters rhyme with “ee”—and not to know what aspects he should focus on.

The further results of this study will be of interest to us. But if there were a medicine to help “reverse” memory and learning deficits, I think that Charlie’s thinking and being would be in many ways the same. He takes in so much of the world around him and I truly think his emotional intelligence is the same as other children his age: As I wrote, my husband Jim has injured his back very seriously and, consequently, has not be able to be at all as active as he is used to and as he loves to be. Jim can barely walk right now (this is my husband who easily runs a mile and a half to train station and through Manhattan streets instead of taking the subway, with a bag stuffed with books and papers). I’ve been explaining to Charlie that his dad injured his back and that Charlie has to do more for himself—-and Charlie has been getting out of bed on his own when I ask (instead of getting tugged and semi-carried; he’s always had trouble getting up in the mornings); he’s pulled on his clothes and grabbed his backpack and run down the stairs for the bus with minimal asking. What is this thing called intelligence, I sometimes wonder?