Enlarge (credit: Getty | RJ Sangosti)

After an MDMA therapy for post-traumatic stress disorder dramatically failed to impress Food and Drug Administration advisers earlier this month, researchers are moving forward with another psychedelic—a slow-release oral dose of the hallucinogenic drug ketamine—as a therapy for treatment-resistant depression.

In a mid-stage, randomized, placebo-controlled clinical trial, researchers tested slow-release ketamine pills, taken twice weekly. The trial, sponsored by New Zealand-based Douglas Pharmaceuticals, found ketamine to be safe compared with placebo. At the trial's highest dose, the treatment showed some efficacy against depression in patients who had previously tried an average of nearly five antidepressants without success, according to the results published Monday in Nature Medicine.

But the Phase II trial, which started with 231 participants, indicated that the pool of patients who may benefit from the treatment could be quite limited. The researchers behind the trial chose an unusual "enrichment" design to test the depression treatment. This was intended to thwart the high failure rates generally seen in trials for depression treatments, even in patients without treatment-resistant cases. But even after selecting patients who initially responded to ketamine, 59.5 percent of the enriched participants still dropped out of the trial before its completion, largely due to a lack of efficacy.

Enlarge / The spliceosome is a large complex of proteins and RNAs. (credit: NCBI)

Almost 1,500 genes have been implicated in intellectual disabilities; yet for most people with such disabilities, genetic causes remain unknown. Perhaps this is in part because geneticists have been focusing on the wrong stretches of DNA when they go searching. To rectify this, Ernest Turro—a biostatistician who focuses on genetics, genomics, and molecular diagnostics—used whole genome sequencing data from the 100,000 Genomes Project to search for areas associated with intellectual disabilities.

His lab found a genetic association that is the most common one yet to be associated with neurodevelopmental abnormality. And the gene they identified doesn’t even make a protein.

Trouble with the spliceosome

Most genes include instructions for how to make proteins. That’s true. And yet human genes are not arranged linearly—or rather, they are arranged linearly, but not contiguously. A gene containing the instructions for which amino acids to string together to make a particular protein—hemoglobin, insulin, albumin, whatever protein you like—is modular. It contains part of the amino acid sequence, then it has a chunk of DNA that is largely irrelevant to that sequence, then a bit more of the protein’s sequence, then another chunk of random DNA, back and forth until the end of the protein. It’s as if each of these prose paragraphs were separated by a string of unrelated letters (but not a meaningful paragraph from a different article).