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The Ups and Downs of New Treatments for Alzheimer’s Disease

August 11, 2020

Two new studies underscore the ongoing challenges of finding effective treatments for Alzheimer’s disease. One study reported that a drug long used to treat Parkinson’s disease may boost the ability of those with Alzheimer’s disease to perform activities like dressing and eating, though further research is needed. The other study found that a form of insulin delivered via the nose, which had shown promise in earlier trials, did not improve memory in people with Alzheimer’s disease, though the device used to deliver the drug may have complicated the results.

For the first study, published in JAMA Network Open, researchers in Italy tested a drug called rotigotine that has been used to treat Parkinson’s disease and restless leg syndrome, a sleep disorder characterized by an excessive urge to move the legs. The drug alters levels of the brain chemical dopamine, which plays a critical role in communication between brain cells.

Dopamine affects a wide array of brain functions. The brain chemical is well known for its role in controlling movement. It is also involved in a number of other cognitive functions, including working memory, learning and decision-making, especially in response to rewards. Correcting dopamine signaling is well known to be beneficial in the case of neurological diseases as well as in normal aging.

The researchers studied 74 men and women with mild to moderate Alzheimer’s disease. About half got rotigotine, delivered via a patch applied to the skin, for 24 weeks. The others got a look-alike skin patch with no drug in it.

The drug did not lead to improvements in memory. But there were hints that it might slow the progression of Alzheimer’s disease to a slight degree, allowing patients to better perform normal day-to-day activities like eating and getting dressed longer than their peers who did not get the drug.

The researchers speculate that the drug, given along with other drugs for Alzheimer’s disease, might lead to improvements in decision-making and other thinking skills that can improve activities of daily living. The drug was well tolerated, with few side effects.

But this was a Phase 2 clinical trial performed on a small number of patients. Larger trials, involving many more patients, must be conducted before researchers will know for sure whether it truly provides benefits for people with Alzheimer’s disease. Many drugs have shown early promise in initial testing, only to be proven ineffective in later-stage trials.

For the second study, published in JAMA Neurology, researchers at multiple medical centers tested insulin, the hormone commonly given to people with diabetes in order to regulate blood glucose levels. The insulin spray is squirted deep into the nose, where it enters the brain via the olfactory bulbs, two brain regions responsible for smell. Intranasal insulin had shown some promise in earlier preliminary studies for improving memory and thinking skills in people with Alzheimer’s disease.

For the study, researchers divided nearly 300 men and women with Alzheimer’s disease or mild cognitive impairment, a memory disorder that often precedes full-blown Alzheimer’s, into two groups. One group got an insulin nasal spray over 18 months, while the others got a placebo nasal spray. Two different spray devices were used during the study to deliver squirts of insulin deep into the nasal passages, where  the fine mist settles and moves directly into the brain along the nerve that transmit smell signals from the nose to the brain.

Results were mixed. When the researchers looked at the overall results, they found that the insulin did not lead to significant improvements in memory or thinking skills, or changes in spinal fluid markers characteristics of Alzheimer’s disease. But when they focused on results from one of the devices, they did note some improvements in symptoms.

The nasal form of insulin, and the devices used to deliver it nasally, are only available in research labs. Nobody is suggesting that anyone go out and inhale insulin, and doctors do not prescribe it; it would not be available in the appropriate form and concentration anyway. But the study results, though modest, support further investigation of the therapeutic value of insulin as a treatment for brain ailments like Alzheimer’s, the authors say.

The findings underscore the continued challenges in discovering effective new treatments against Alzheimer’s disease. These two studies also show the continued ramifications of research conducted by The Fisher Center for Alzheimer’s Research Foundation. The late Dr. Paul Greengard, longtime leader of the Fisher Center lab, received the Nobel Prize for his work related to dopamine signaling that he conducted in the 1970s through the ’90s, in the hopes that ongoing research will one day lead to a cure for Alzheimer’s disease.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Sources: Giacomo Koch, MD, PhD; Caterina Motta, MD; Sonia Bonni, PhD; et al: “Effect of Rotigotine vs Placebo on Cognitive Functions Among Patients With Mild to Moderate Alzheimer Disease: A Randomized Clinical Trial.” JAMA Network Open, July 15, 2020

Suzanne Craft, PhD; Rema Raman, PhD’ Tiffany W. Chow, MD; et al: “Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial.” JAMA Neurology, June 22, 2020

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