http://www.northwestneurology.net/sc...nson-patients/


After analyzing cells and postmortem brain tissue from animals and humans, researchers noted that oxidative stress—a known culprit in neuron death—activated the protein tyrosine kinase c-Abl in the nigra-striatum area of the brain. Neurons in this part of the brain are particularly vulnerable to Parkinson disease injury.

Activation of this protein led to changes in the parkin protein, which is known to be mutated in hereditary Parkinson disease. The altered parkin lacked the capacity to break down other proteins, leading to harmful clumps of unprocessed protein in the neuron. The scientists believe this accumulation leads to progressive neuron death, resulting in Parkinson symptoms that worsen over time.

“When we blocked tyrosine kinase c-Abl activation, parkin function was preserved and neurons were spared,” Dr Imam said. “We believe these studies provide sound rationale for moving forward with a preclinical trial of tyrosine kinase c-Abl inhibitors, with the goal of developing a potent therapeutic drug for slowing the progression of Parkinson’s.”

If preclinical trials in animal models of Parkinson disease yield positive results, the next step would be clinical trials in human patients, Dr Imam said.

Tyrosine kinase c-Abl inhibitors are approved by the FDA for treating myeloid leukemia and gastrointestinal tumors. This could speed approval of the drug for Parkinson disease and its translation from bench research to clinical practice.

Yes, this is great news for the reported 5% who have Parkin mutations, what happens to the rest of us? How is it that scientists extrapolate a potential genetic Parkinson's "cure" or disease altering treatment to the idiopathic majority when they do not know whether we even have Parkin dysfunction? We are shut out of genetic testing.

Sorry, Soccertese, not picking on you, just am fed up with this trend of using genetics that apply to a select few but then used as basis of new treatment for all.

James Watson (of DNA famed team Crick & Watson) just published a scathing criticism of the Cancer research establishment and pointed to that very same "trend" to misapply genetic discoveries:


A number of Watson’s disgruntled colleagues have already begun to rally behind him in recognition of the disappointing results of the past several decades of cancer research. And the problem, they believe, has been the narrow focus on finding individual genetic signatures for each individual type of cancer and then attempting to base cures on these.



More of Watson' critique here: http://www.redorbit.com/news/health/...search-011013/

Plug in Parkinson's for Cancer; our researchers seem to be doing the same thing. Sorry to be an Oscar the Grouch on this, but I think it highly irresponsible of scientists to make these leaps when they have no clinical premise for it to actually work as a treatment for all causes of PD. I would not get so irked if they actually acknowledged that they have yet to learn if the majority PD'ers share a similar Parkin dysfunction. I would think that has to be established before we see human trials. Maybe I am missing something but to me it looks like a crap shoot.

Laura

my interpretation is they offered a possible explanation how oxidative stress can indirectly affect the normal parkin protein in pd'ers without the parkin mutation.

i didn't see anywhere where they were looking at cells that had the parkin mutation.
what i don't understand is how they treated human cells, were they cell lines?

regardless, the research tools ARE GETTING BETTER.

Agreed that the research tools are better. I definitely need to chill out; I didn't read it carefully enough to spout off. However, does this explain how we lose even more neurons in our locus coeruleus? In my mind, linking anything to gene mutations and only dopamine in the substantia nigra is just too narrow anymore. Of course, I would love it if things were that simple, but we have a lot of catching up to do in research on the loss of norepinephrine in PD.

Here is an interesting article kinda tying things together.

Oxidative Stress, DNA Damage, and c-Abl Signaling: At the Crossroad in Neurodegenerative Disease

Oh, good question on the cells. Looks like cultured cell lines... here is a link to the original article

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039694/

Laura