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Sunday, August 7, 2022

Academics & Research

Prof pioneers receptor based drugs


A research team that includes a professor at UH’s Center for Nuclear Receptors and Cell Signaling is endorsing a new approach to producing drugs that treat cancer, Alzheimer’s disease and multiple sclerosis.

CNRCS director Dr. Jan-Åke Gustafsson’s efforts focus on the study of nuclear receptor transcription factors. These are proteins found within cells that regulate and control the flow of genetic information.

“What makes these receptors particularly interesting is that their activities are regulated by compounds that we can administer to the cell,” Gustafsson said.

Gustafsson said this attribute makes receptors “drugable,” which attracts the drug industry to target these receptors.

“They are actually acting through the receptors,” Gustafsson said.

Estrogen receptors are where Gustafsson’s interest primarily resides.

He was involved in the discovery of estrogen receptor beta in 1996 at Karolinska Institute in Sweden, squashing the notion that only one estrogen receptor type — estrogen receptor alpha — existed.

“It turns out that these two receptors have a very interesting relationship that could be described as yin and yang,” Gustafsson said.

One of the main qualities of estrogen receptor alpha is that it stimulates proliferation, an increase in cell number by division. This can lead to early stages of cancer if over expressed. However, estrogen receptor beta is “anti-proliferative,” acting as an inhibitor. This is being investigated as a possibility to treat breast, prostate and colon cancer.

He said treatment of diseases quite different from cancer is possible. The activation of estrogen receptor beta can limit the buildup of amyloid, a protein that plays a role in Alzheimer’s and other neurodegenerative diseases. It can also stimulate oligodendrocytes — cells that are responsible for creating a fatty layer to help neurons carry electrical signals — which are lacking in multiple sclerosis patients.

The process for developing these drugs includes clinical trials and addressing potential side effects, which makes it lengthy.

“After an original discovery of a new drugable target, it takes about 20 years before it is on the market for patients to buy,” Gustafsson said.

Progress is also being made on the research of another transcription factor, liver x receptor beta. This receptor is activated by cholesterol. Gustafsson said he believes liver x receptor beta is also involved with certain diseases in the central nervous system. However, he said it seems they are further along in their estrogen receptor research.

Gustafsson collaborates with other scientists at UH as well as scientists at the Methodist Hospital Research Institute.

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