Blocking c-Abl Halts Parkinson's Progression in a Mouse Model of the Condition
Using a mouse model of Parkinson's disease, researchers here demonstrate that an enzyme called c-Abl is associated with the accumulation of misfolded and toxic α-synuclein that is involved in the progression of this degenerative condition. They manage to halt the progression of Parkinson's symptoms, which is a promising sign when accompanied by supporting evidence to the degree it is here:
Researchers say they have gleaned two important new clues in the fight against Parkinson's disease: that blocking an c-Abl prevents the disease in specially bred mice, and that a chemical tag on a second protein may signal the disorder's presence and progression. Autopsies have revealed that c-Abl is especially active in the brains of people with Parkinson's disease, a progressive disorder of the nervous system that affects movement. Additionally, studies in mice bred to be prone to the disease found drugs that block c-Abl may prevent or slow it. But, the drugs used in those studies could also have been blocking similar proteins, so it wasn't clear that blocking c-Abl was what benefited the animals by either preventing symptoms or influencing disease progression.
The researchers' new experiments started with mice genetically engineered to develop the disease and knocked out the gene for c-Abl, a move that reduced their disease symptoms. Conversely, genetically dialing up the amount of c-Abl the mice produced worsened symptoms and hastened the disease's progression. Increasing c-Abl production also caused normal mice to develop Parkinson's disease. To learn more about how that happened, the team took a look at how c-Abl interacts with another protein, α-synuclein. It's long been known that clumps of α-synuclein in the brain are a hallmark of Parkinson's. The researchers found that c-Abl adds a molecule called a phosphate group to a specific place on α-synuclein, and that increasing levels of c-Abl drove more α-synuclein clumping along with worsening symptoms. "We plan to look into whether α-synuclein with a phosphate group on the spot c-Abl targets could serve as a measure of Parkinson's disease severity." No such objective, biochemical measurement exists now, which hampers studies of potential therapies for the disease.
I just checked the prices for Nilotinib, a C-Abl inhibitor. 28 capsules only cost around 2800 USD...