The LA Times reports on research looking at the use of pentylenetetrazole for Down Syndrome:
Lab mice with the mental retardation of Down syndrome got smarter after being fed a drug that strengthened brain circuits involved in learning and memory, researchers reported Sunday. After receiving once-daily doses of pentylenetetrazole, or PTZ, for 17 days, the mice could recognize objects and navigate mazes as well as normal mice did, researchers said. The improvements lasted up to two months after the drug was discontinued, according to the report in the journal Nature Neuroscience.
Senior study author Craig C. Garner, a Stanford School of Medicine professor, said his lab was preparing to conduct human trials of the drug, although he said it would take time to complete more preliminary studies and procure a supply of purified PTZ. People with Down syndrome should not be given the drug until it has been studied further, he cautioned, because PTZ can induce seizures at high doses and might have other serious side effects.
Down syndrome is a genetic disorder caused by an extra copy of chromosome 21. The syndrome occurs in one of 660 births and usually causes cognitive deficits, cardiac problems and physical abnormalities, such as low muscle tone, short stature and an upward slant to the eyes. More than 300,000 Americans have Down syndrome, making it the leading cause of mental retardation. There is no approved drug to improve cognition in people with Down syndrome.
PTZ blocks a neurotransmitter called gamma-aminobutyric acid, researchers said. GABA, as it is called, passes messages between neurons along specific brain pathways. Normal brains have a balance of neurotransmitters that excite neurons and make learning possible, and of GABA, which slows neurons down so they do not become overly stimulated. It is believed that people with Down syndrome have too much GABA, inhibiting brain circuits involved in learning and memory.
The drug was used until 1982 to enhance cognition in the elderly and mentally impaired people, but was removed from the market by the Food and Drug Administration because studies showed no clear benefits. Garner said he believed the drug failed in part because the dosing schedule then was different from the one his team used in mice.The mice were genetically altered to possess cognitive impairments similar to those of Down syndrome patients
Mice brains are a lot different from human brains, and I am skeptical of this drug's ability to make much of a difference in the intellectual functioning of persons with Down Syndrome. I tried to look up some of the old literature from the 70's on pentylenetetrazole, unfortunately, Pub Med does not have abstracts online from this time period. The next time I'm at the medical library, I'll look up some of the articles.
Monday, February 26, 2007
Saturday, February 24, 2007
Autism has been in the news a lot recently. Risperidone is now approved for the treatment of pediatric autism. This creates the unusual situation in which a drug is approved for a childhood disease, but not the same disease in adults. Usually it's the other way around.
It seems that every day there's a new study showing increasing rates of autism. In my opinion, there are 2 reasons for this:
1) Many studies are now looking at "Autistic spectrum disorders," which include less severe variants of Autism such as Asperger's Disorder.
2) Some parents are pushing for the diagnosis of Autism for their child, because children with autism are generally elgible for higher levels of services than children with (isolated) mental retardation. There is a great degree of comorbidity between autism and mental retardation, and some children who would have just received the diagnosis of mental retardation in the past now also receive the diagnosis of autism.
I don't treat children, but I treat many adults with mental retardation, some who also have autism. I don't understand why autism is on axis I and mental retardation is on axis II of DSM-4, TR.