Alzheimer’s disease currently affects around 44 million people worldwide. The disease destroys cells in the brain, inducing symptoms such as memory loss, mood swings, poor judgement, and a shortened attention span. The number of Canadians suffering from this debilitating illness is rising, but no cure or treatment currently exists to alleviate their suffering. A team of McGill researchers led by Dr. Claudio Cuello, a professor in McGill’s Department of Pharmacology and Therapeutics, is attempting to change this grim reality. 

Their research has shown that, in small doses, the metal lithium is capable of reducing Alzheimer’s symptoms and could prevent the emergence of Alzheimer’s in people with a genetic predisposition to the disease.  

Lithium has long been used in the medical field to treat mood disorders such as bipolar depression. However, conventional lithium solutions have a very narrow therapeutic window and carry severe side effects that prevent their long-term use in elderly patients. Side effects include nausea; tremor; weight gain; polyuria, a condition when a person’s body urines more than normal; and polydipsia, or excessive thirst. 

Cuello and former PhD student Edward Wilson instead turned to NP03, a new low-dose lithium formulation created by a French pharmaceutical company that avoids the negative side effects associated with conventional lithium. The NP03 preparation traps a compound called lithium citrate within another material in a process known as nanoencapsulation. NP03 has previously been shown to protect mice from neurological effects associated with Huntington disease.

“Compounds [that] are lipidic in nature pass more readily [through the blood-brain barrier],” Cuello said in an interview with The McGill Tribune. “This nanoencapsulation is a […] lipidic trapping formulation […] that allows us to use doses [that] are at least 200 times lower than the conventional lithium.”

Cuello and his team conducted an animal study to test the effectiveness of NP03 against Alzheimer’s. They administered the NP03 formula to genetically-modified rats with the amyloid precursor protein (APP) gene. APP is the hallmark of Alzheimer’s disease in humans. 

“We [reduced the symptoms] at fairly advanced stages [and found that] the cognitive impairments induced by the [lithium] therapy were spectacularly positive,” Cuello said.

Indeed, the NP03 treatments reduced levels of amyloid plaques—aggregated proteins that are thought to disrupt cell connections—and reversed memory deficits in the rats. Yet the treatment cannot remedy the symptoms of Alzheimer’s once severe cognitive decline has set in; it is only effective in low doses over sustained periods before dementia symptoms appear.

“[If a person has] a profile [that] is Alzheimer’s-like and [their] cognition is going down, this is in my view, and in the view of many, a perfect opportunity to start therapy before the structural changes in the brain are such that they will be totally irreversible,” Cuello said.

The next step for Cuello and his team are human trials. 

“[The human trial] opportunity is with Down syndrome [patients],” Cuello said. “We can anticipate in cohorts of Down syndrome [patients] when the Alzheimer’s [symptoms are] activated.”

Individuals with Down syndrome are perfect candidates because they have a triplication of the gene carrying the APP protein. 

“Down syndrome [patients] have trisomy on chromosome 21, which causes the typical syndrome, but […] it means duplication of a protein called amyloid precursor protein,” Cuello said. 

Due to increased levels of APP, Down syndrome patients nearly always develop Alzheimer’s symptoms at an early age, making the onset of the disease more predictable and the importance of the trial succeeding in treating such symptoms even greater. 

Cuello believes that, in the next few years, it will become possible to understand early stages of the disease and successfully treat it. For the first time, there is hope for the millions of people suffering from Alzheimer’s disease. 

“I’m optimistic,” Cuello said. “I think we are at the verge of great discoveries in Alzheimer’s.”