Growing new brain cells to treat depression: A clinical trial

MIT Tech Review reports that a San Diego-based pharmaceuticals company BrainCells Inc. is carrying out a phase II clinical trial to test the efficacy of a neurogenesis-stimulating compound as a treatment for depression.

It has been known, for about 20 years, that the brains of mammals (including humans) contain stem cells which are capable of dividing to generate new neurons. This process, called neurogenesis, occurs throughout adulthood in several discrete areas of the brain (the hippocampus and olfactory bulb), but the exact function of the newly-generated cells remains unclear.

Reduced neurogenesis has been implicated in various conditions, including depression. Neuroimaging studies show that the hippocampi of depressed patients are reduced in volume. Different classes of antidepressants, for example tricyclics and specific serotonin re-uptake inhibitors stimulate neurogenesis, and may therefore slow or reverse this volume loss.

Antidepressants appear to stimulate the birth of new neurons indirectly, via a number of different mechanisms. Their neurogenic properties were discovered by chance only very recently, long after they came into use. With this in mind, the researchers at BrainCell, Inc. adopted the reverse approach, reasoning that drugs which stimulate neurogenesis directly may be effective as antidepressants.

The compound currently being tested by BrainCells Inc. is a small molecule called BCI-540, which emerged as the best candidate following screens carried out on nerve cells grown in Petri dishes. BCI-540 has proven to be effective in animal models anxiety, and, in the first clinical trial, which involved 700 patients and was carried out earlier this year, it was found to produce none of the side effects commonly associated with antidepressants.

The current trial is based on the assumption that antidepressants are effective because of their ability to promote neurogenesis in the hippocampus; however, it has not yet been confirmed that this is the case. Even so, BCI-540 has apparently been shown to reduce anxiety in animals, so the researchers from the company are planning to test the effectiveness of the compound in treating post-traumatic stress disorder (PTSD).

Drugs that stimulate neurogenesis could possibly prove to be effective in treating a number of neurological conditions, such epilepsy, stroke, and Parkinson's and Huntington's diseases. To date, most of the research into treatments for these conditions has focused on replacing lost or damaged neurons by implantation of embryonic stem cells, because stimulating the brain's endogenous stem cells to generate new neurons has proved extremely difficult.

When taken by healthy people, neurogenic compounds could also enhance cognitive processes such as learning and memory, which are dependent on the hippocampus. BrainCells Inc. is testing another compound, BCI-632, for its ability to enhance cognition. This compound is the most neurogenic one they have identified yet in their screens. It has been shown to enhance at least one type of memory in rodents, and the company hopes to begin human trials next year.

(Image of hippocampal neurogenesis from BrainCells, Inc. Neural stem cells are stained red, newly-generated cells orange.)

Related:

• Neurogenesis in the adult human brain