Approved drugs are to be studied for use in Alzheimer’s disease

Many drugs that have been approved by the Food and Drug Administration could be repurposed or used off label to treat Alzheimer’s disease, according to reports from the Alzheimer’s Drug Discovery Foundation conference in New Jersey.

The foundation is supporting 18 approved drugs in repurposing trials. This brings the total number of approved drugs that were being studied for use in treating Alzheimer’s disease in repurposing trials to at least 127, the foundation said.

The drugs discussed at a press briefing on 13 September were tadalafil (Cialis), approved to treat erectile dysfunction, and levetiracetam (Keppra), approved to treat epilepsy.

Atticus Hainsworth of St George’s, University of London is leading a double blind, placebo controlled crossover study of tadalafil in men and women who have symptomatic small vessel disease in the brain but have not been diagnosed with vascular cognitive impairment.

Hainsworth said that a chronic lack of blood flow to deep brain areas was common in Alzheimer’s disease and other dementias, leading to vascular cognitive impairment. Vasodilation of small cerebral arteries could improve blood flow and treat, prevent, or postpone vascular cognitive impairment. The study will see if tadalafil increases blood flow to deep brain areas. Tadalafil crosses the blood-brain barrier, unlike other erectile dysfunction drugs. In the study it was given at an oral dose of 20 mg, higher than the dose used to treat erectile dysfunction.

Sharon Rosenzweig-Lipson, of AgeneBio in Baltimore, described a small clinical trial re-purposing the anti-epileptic agent levetiracetam (Keppra) in people with mild cognitive impairment, the earliest symptomatic stage of Alzheimer’s disease in which patients have memory loss.

Rosenzweig-Lipson said that a randomized, placebo controlled Phase 3 trial had been designed which would involve 830 patients and last 18 months. The study would use a lower dose (220 mg) than that used to treat epilepsy.

Howard Fillit, chief science officer of the Alzheimer’s Drug Discovery Foundation, said that the foundation’s sole aim was to find and develop new drugs to treat Alzheimer’s disease. It worked to fill the funding gap between basic research and clinical development by finding and supporting promising discoveries and pre-clinical development. Fillit is also a clinical professor of geriatrics and palliative medicine at Mt Sinai Medical Center in New York.

Besides the two drugs discussed at the briefing, the foundation was also supporting clinical trials of 16 other drugs that might be repurposed for use in the treatment of Alzheimer’s disease. Many were international, multi-center trials that focused on patients with early disease. Among the 16 drugs were the selective norepinephrine uptake inhibitor atomoxetine (Strattera), prescribed for childhood attention deficit hypersensitivity disorder; the thiamine derivative benfotiamine; the angiotensin II receptor blocker candesartan (Atacand); and the dopaminergic agonist rotigotine (Neupro).

About 5 million people in the US have Alzheimer’s disease and it is now the sixth leading cause of death—although, according to the National Institute of Aging, recent estimates say it may actually rank third.