Two short chains of amino acids could pave the way for new treatments

Two years after discovering a way to neutralize an undesirable protein linked to Alzheimer's disease, Jack Jhamandas, a distinguished professor at the University of Alberta and neurologist, discovered a new piece of the puzzle. Alzheimer's that would bring him closer to the treatment of the disease.

In a study published in Scientific reportsJhamandas and his team discovered two short peptides, or amino acid chains, which, injected daily into mice with Alzheimer's disease for five weeks, dramatically improved the memory of the mouse. The treatment has also reduced some of the harmful physical changes in the brain associated with the disease.

"In the mice that received the drugs, we found less amyloid plaque accumulation and a reduction in brain inflammation," said Jhamandas, also a member of the Institute of Neuroscience and Disease. Mental Health.

"So it was very interesting and exciting, because it showed us that not only was memory improved in mice, but that the signs of brain pathology related to Alzheimer's disease were also greatly improved. a surprise for us. "

S & # 39; s relying on previous research

This discovery builds on previous discoveries of a compound called AC253 capable of blocking the toxic effects of a protein called beta-amyloid, which would greatly contribute to Alzheimer's disease because it is often found in large numbers in the brains of patients with the disease. . The AC253 prevents beta-amyloid from attaching itself to certain receptors in brain cells – a process that Jhamandas equates to obstruction of a keyhole.

However, while it has been shown that AC253 prevents beta-amyloid accumulation, it is not very effective at reaching the brain and is rapidly metabolized in the bloodstream. As a result, treatment using AC253 requires the effectiveness of large amounts of the compound, which is impractical and increases the chances that the body develops an immune response to the treatment. Turning the AC253 from an injectable drug into a pill would solve metabolism problems and increase efficiency, but the AC253 was too complex to be able to produce an oral drug effective.

Jhamandas' solution was to cut AC253 into pieces to determine if it could create smaller peptide chains blocking beta-amyloid in the same way as AC253. Through a series of tests using mice genetically engineered to carry Alzheimer's disease, the Jhamandas team discovered two shorter pieces of AC253 that mimicked the preventative and restorative abilities of the larger peptide.

New drug under development

After identifying the short peptides, Jhamandas and his team, including renowned virologists, Lorne Tyrell and Michael Houghton, used a computer modeling and artificial intelligence process to discover a small molecule drug, similar to the drugs used to treat high blood pressure or cholesterol. it is developing now.

The team is focusing on making an optimized and oral version of the drug so that clinical trials can begin, said Jhamandas, who added that small molecule drugs are preferable for treatment, especially for drugs because they are less expensive. orally and can more easily reach the brain through the blood, said Jhamandas.

Although Jhamandas is optimistic about the potential of his new drug to change the management mode of Alzheimer's disease, he does not hesitate to highlight the years of research that he and others researchers have accomplished to arrive at this stage.

"It has been 15, 20 years of painstaking and progressive work," he said. "And it's like building a house: you put one brick, then you put another, and very quickly, you have a foundation and you have a house.

"Sometimes you discover a discovery that could potentially fundamentally change the game, like hitting a homerun, and I'm very happy that we really have something to do here."