Alzheimer's: the hope given by French research
Pr Beaulieu and his team have just discovered a potentially active protein against disease.
This is a new path for a pathology that now reaches 800,000 people in France and that no treatment has so far slowed down. A protein naturally present in the brain, called FKBP52, may be able to fight against Alzheimer's disease, according to preliminary work published Monday in the minutes of the American Academy of Sciences (PNAS) by the team of the Pr Etienne-Emile Baulieu. At 83, the tireless endocrinologist and biochemist, famed for his discoveries about DHEA and the abortion pill RU486, continues his research on aging. Since 2008, he has chaired an institute whose ambition is to "help, thanks to biomedical research, to delay the moment of dependence".
The brain of Alzheimer's patients is characterized by two types of lesions: on the one hand deposits of beta-amyloid protein plates around the neurons; on the other hand the accumulation of tau protein in these cells, which alters their functioning. So far, it is mostly the beta-amyloid track that has been explored to develop treatments. With a number of failures, and a lot of trials going on, especially with vaccines. Researchers are also looking into tau protein abnormalities, which are also implicated in other brain degenerations. But for now, only one "anti-tau" drug, Rember, has been tested in patients. This is also the path that Professor Baulieu tackles with his FKBP52. Discovered and cloned by his team around 1992, this substance belongs to the family of immunophilins, proteins that bind to certain immunosuppressive drugs. The large presence in the brain of FKBP52 had suggested to the researcher that this protein may have other functions than immunological.
In 2007, Étienne-Émile Baulieu and Béatrice Chambraud (Inserm) discovered that this protein interacts with brain microtubules - small channels essential for the proper functioning of neurons and the communication of these cells. They have just taken a new step by demonstrating on cells that FKBP52 can actually block the deleterious developments of tau (which clings to microtubules). For Professor Baulieu, it is a new hope to try to curb or correct tau protein abnormalities. He is now considering testing this approach on animal models of Alzheimer's disease, through collaborations with British and Australian teams.
"Our research also opens possibilities for early diagnosis of the disease, biochemical abnormalities being present at least five to ten years before the clinical signs," says the researcher. Dr. Claude Sebban (Charles-Foix Hospital, Ivry) confirms that collaboration is being established with the Institut de longevité de Paris, particularly to develop methods of dosing. "This work, very basic, is not a demonstration of an effect of this protein on Alzheimer's disease," says Pr Philippe Amouyel (Inserm), which drives the research component of the Alzheimer's plan. Professor Jean-Marc Orgogozo (neurologist, Bordeaux), however, considers "a priori, it is a path that deserves to be explored." So far, according to him, the track of tau protein has been under-researched. However, he notes that the development of the first anti-tau molecule (which clinical trials were promising in 2008) is currently at a standstill, due to lack of funding to continue testing. Convinced that FKPB52 should be continued, Professor Baulieu calls for private funding. Pierre Berger has already committed to finance his work.