La Jolla biotech firm looking at obesity connection to Alzheimer’s

INmune Bio Chief Executive RJ Tesi

La Jolla-based INmune Bio is exploring the connection between obesity and Alzheimer’s disease.

Chief Executive Dr. RJ Tesi said the immuno-oncology company is looking at chronic inflammation, which, when present with neuroinflammation, can contribute to conditions such as Alzheimer’s.

Though chronic inflammation “sounds as benign as white bread,” it is “a terrible disease that many of us have,” Tesi said.

Unlike acute inflammation, which occurs when someone gets, for example, a splinter, chronic inflammation is the result of a combination of factors such as genetics and lifestyle.

“Chronic inflammation is this slow, grumbling burn that is killing us,” Tesi said. “You can’t see it, you can’t feel it, you can’t test for it.”

But, he said, “metabolic problems such as obesity actually contribute to this. The inflammation of fat cells spills over and … you get inflammation in your body and that inflammation spreads and affects the brain.”

From there, the inflammation can affect the synapses that allow nerve cells in the brain to communicate.

“There are cells in the brain called glial cells that make up 70 percent of your brain,” Tesi said. “They don’t store your piano lessons or your boyfriend’s birthday — they are all about the care and feeding of nerves cells. And synapses are like the wires between nerve cells. You need both healthy nerve cells to store the information and healthy synapses so the nerve cells communicate.

“When you get chronic inflammation and neuroinflammation, the nerve cells start dying off and the synapses start getting disrupted so they can’t talk to each other. That combination of nerve cell loss and lack of communication is what gives you Alzheimer’s.”

The research that led to the discovery was conducted by INmune Bio researcher Dr. Malú Tansey.

Her experiment involved feeding mice a high-fat, high-fructose diet and not letting them exercise, then studying different biological functions and running memory tests. A peer-reviewed paper from Tansey on neuroinflammation and obesity was recently published in Alzheimer’s Research & Therapy.

“She showed if you have obesity, you have an increased risk of inflammation peripherally, and that creates an increased risk of inflammation centrally,” Tesi said.

Just as it takes years for this type of inflammation to develop, it would take years to prevent.

“If you are 78 and have lived a life of debauchery, you can’t say, ‘Tomorrow I’m going to eat better so I don’t get dementia.’ That horse has probably left the barn,” Tesi said. “It’ll help, but it’s certainly not going to go away. There are lifestyle things that can help. … But the problem with lifestyle changes, it is very hard to implement. If you start young … there is no question that lifestyle helps. But most of us cannot change enough of our lifestyle. People would much rather take medicine than go to the gym every day.”

As to where the research goes from here, Tesi said the company is looking to treat Alzheimer’s in the near term to prevent it from getting worse, but the long-term goal is preventing people from getting it at all.

“That is going to take some time,” he said. “But the future is that we will make the whole concept of Alzheimer’s disease obsolete. That is the goal. Wouldn’t that be great?” ◆