Alzheimer's disease - leteprinim
The increasing average age of the population in the western world means that the incidence of diseases and conditions that affect old people is rising.
The increasing average age of the population in the western world means that the incidence of diseases and conditions that affect old people is rising.
In particular, Alzheimer's disease is likely to be an increasing problem. The precise cause of Alzheimer's is unknown, but it is certainly linked with damage to the cholinergic neurons in the cortex and hippocampus in the brain. This results in a lowering of the levels of acetylcholine, and the physical and mental activity of the patient are adversely affected. Some medicines that provide short-term clinical improvement are available, and these concentrate on restoring the levels of acetylcholine in the brain, and compounds that inhibit the activity of acetylcholinesterase, the enzyme that breaks it down, predominate.
A novel potential treatment for Alzheimer's is being developed by NeoTherapeutics. The drug, leteprinim, has been shown selectively to increase levels of the enzyme heme oxygenase-1 in neurons in the brain that are involved in memory. The action of this enzyme leads to the production of carbon monoxide, which acts as a neurotransmitter and is believed to be involved in memory. Animal models showed that it is biologically active in neuroprotection, it releases neurotrophic factors and it stimulates stem cell proliferation.
Leteprinim showed promising results in a Phase II trial. A total of 431 patients started the 90 day trial, and 389 of these completed the course.1 Patients in the placebo controlled trial received the drug as a once daily, berry flavoured oral suspension and showed a statistically significant improvement in their neuropsychiatric inventory rating, a recognised test that measures behavioural symptoms such as psychosis, aggression and hallucinations. Similar adverse event profiles were reported for those given leteprinim and placebo.
A Phase II trial has recently been completed. In a double blind, placebo controlled trial, 521 patients were given 500mg leteprinim or placebo twice a day for a week, followed by 1,000mg of leteprinim or placebo twice a day for 11 weeks. However, the results were not sufficiently statistically significant, and further trials are under way. The drug is also being evaluated for the treatment of Parkinson's disease, spinal cord injury and chemotherapy induced neuropathy.