The hormone insulin, administered via a nasal spray, is being investigated as a treatment for Alzheimer’s disease. While insulin is best known for its role in regulating blood sugar, it also is thought to play a role in Alzheimer’s, having shown reduced levels of insulin and insulin signaling in patients’ brains.

Administering insulin as a nasal spray allows the hormone to enter the bloodstream via the small blood vessels in the nose and to go directly to the brain, bypassing the peripheral bloodstream. This prevents it from lowering the patient’s blood sugar.

How nasal insulin works

Insulin’s role in the brain is not fully understood, but there is growing evidence suggesting it may play a role in Alzheimer’s disease.

For example, Type 2 diabetes, which is defined by insulin resistance, significantly increases a person’s risk of developing Alzheimer’s.

Moreover, insulin may be involved in clearing beta-amyloid from the brain. Beta-amyloid is one of the proteins that accumulate in the brains of Alzheimer’s disease patients, causing brain damage. In vitro experiments suggest that exposing nerve cells to beta-amyloid in the laboratory reduces the number of insulin receptors they produce, making them less sensitive (or more resistant) to insulin.

Insulin also appears to have effects on memory in healthy brains. One study showed that nasal insulin increased memory performance in young adults. Because reduced insulin or reduced responsiveness is associated with Alzheimer’s, it is hoped that increasing the amount of insulin in the brain might alleviate the symptoms of the disease.

Nasal insulin in clinical trials for Alzheimer’s disease

Nasal insulin has been tested in several Phase 2 clinical trials in patients with mild cognitive impairment or early Alzheimer’s. Both short-term (three weeks) and long-term (four months) treatments with nasal insulin resulted in improved memory and everyday function. The longer term treatment preserved cognition as measured by a common Alzheimer’s assessment test called ADAS-cog.

However, evidence suggests that nasal insulin may not be equally effective in all Alzheimer’s patients. Response to nasal insulin may depend not only on dose, but also on what form of the APOE gene the patient carries. (The so-called e4 version of the gene is known to increase a person’s risk of developing late-onset Alzheimer disease).

Two clinical trials are currently testing nasal insulin as a treatment for Alzheimer’s disease. The first, which is no longer recruiting participants, is a year-long Phase 2/3 trial (NCT01767909) looking at the therapeutic effects of nasal insulin in patients with amnestic mild cognitive impairment or mild Alzheimer’s disease. This study is active and is expected to be completed by the end of 2018.

The second, a Phase 1 trial (NCT02462161), is examining the effects of a fast-acting form of nasal insulin (insulin aspart) on cognition, daily function, and blood and cerebrospinal fluid markers of Alzheimer’s disease, as well as beta-amyloid deposition in the brain. Participants must be at least 50 years old and have a diagnosis of mild cognitive impairment or Alzheimer’s. The trial is recruiting participants in North Carolina and runs 12 weeks. Participants will receive either insulin aspart, or a placebo, twice a day.

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