Michael J. Fox Foundation Funds AFFiRiS AG to Develop Parkinson's Vaccine

VIENNA, December 16, 2010 /PRNewswire/ -- With a grant of USD 475,000, the Michael J. Fox Foundation is funding preclinical development of a vaccine against Parkinson's disease by AFFiRiS AG. The vaccine, known as PD01, targets the protein alpha-synuclein and might offer for the first time a possibility for a treatment that can slow or stop the progression of Parkinson's disease. The basis of PD01 is the company's AFFITOME(R) technology, which already delivered, among others, two vaccines from AFFiRiS AG for the treatment of Alzheimer's disease.

Affiris is not the only company working on a PD vaccine...and I dont' know if the medical establishment has confirmed whether the synuclein placques are harmful or protective? I've done a lot of research on these placques and most agree that these placques are not seen in the majority of people without PD (but some people do have them, but never showed symptoms of PD during their life), but this does not answer the question of whether the placques form as a result of the PD process and are harmful, or whether they might be a response designed to be protective.

Showing my ignorance here. But just because your body has something in it that most others don't does not mean it's the bad guy and the underlying cause of the whole problem...a higher white blood cell count than normal (when you are sick) is an example.

Ok, all you scientist please explain to me how a vaccine can be devloped when they still do not know the cause of PD?

I am not being critical or wanting to be disruptive, did I miss something?

[QUOTE=GregD;726832]Ok, all you scientist please explain to me how a vaccine can be devloped when they still do not know the cause of PD?

I am not being critical or wanting to be disruptive, did I miss something?[/Q

Greg,
We don't know what causes PD, but whatever is the agent, it has a profound effect on alpha synuclein. Alpha-syn is chaperone molecule in the neurons, likely to be involved in the transport of other molecules (unknown at this point>>) and its natural state is monimeric, i.e. like a single piece of thread. Mutations and chemicals cause this protein to aggregate (sort of knotted thread) and this aggregated form cannot be cleared by the cell and accumulates and does a lot of damage to neurons. Also this aggregated form of alpha-syn activates microglia, induces inflammatory cytokines and all these cause neuroinflammation.

So for vaccine development there are a couple of strategies. 1. If alpha-syn aggregation is prevented/at least slowed down, there is a possibility for decreased neuroinflammation and slowing down the pace of progression. If a vaccine were to be used as a preventive one, I am guessing that it would prevent alpha-syn from forming multimers/aggregates
Other strategy probably is that a PD vaccine generates good immune cells (Treg) that would prevent the activation of microglia and inflammation.

I am not sure of the exact way this company is taking to develop a vaccine, but the strategy seems to be preventing/slowing down neuroinflammation one way or other. Vaccines as of now, do not prevent PD, but if PD is initiated, they will halt the progression at an early stage.
This is what I understand from my reading. Hope this answers your questions.

Girija

I guess I am wondering if Affiris in providing proof of concept, which it obviously has, has also provided more substantial evidence that PD most likely begins as auto immune reaction that turns pathological?

Girija is by far the expert here, but I wanted to try to add a little more to the discussion. Lurking, like Girija has said we all normally make alpha-synuclein, but in PD it aggregates in our SN and becomes toxic. Researchers do not know whether the aggregation is a result of the PD toxic cascade or whether it is key to genesis of the toxic cascade though I think more evidence is mounting on the idea that the protein is a key agent in starting the process especially since is now proven that a genetic mutation exists that results in abnormal proliferation of a-synuclein and many patients with PD test positive for antibodies to the protein. Please jump in and correct me, but I think we would only show anti bodies to a-synuclein if it were targeted by our immune system as somehow toxic, and it would not be that way at normal levels. So in my mind the anti body shows that the protein is definitely considered toxic; I am not sure whether this supports the idea that the protein is an instigator in the disease process or not. Further, a-synuclein clumps result in Lewy Bodies which are the hallmark of PD. Yet, interestingly, they are finding cases of PD without the presence of Lewy Bodies and also that Lewy Bodies show in 15% of brains considered PD free. What exactly does this mean?

Girija, I have read that in this vaccine they hope to redirect T cells toward out of control protein aggregation. In mouse models, this has halted disease progression and in very early stages reversed it. In my mind that reversal says "cure" but it really offers something to everyone. In healthy people it means prevention, and in us hopefully halts the process or at least slows it down. Affiris has also met proof of concept meaning that the underlying theory also works in humans and that it is a sound treatment approach.

Is it possible to do this without the assumption that PD is auto immune based?

The fact that the University of Nebraska is also in hot pursuit of a vaccine says that researchers are onto something big.

I just don't understand why people are not more excited by this. At the very least it is a water shed in that it is the first time researchers have targeted the root cause of PD merely than just passively looking at symptom management.

Laura

Here is some more up to date info from University of Nebraska. They are also working on a vaccine interrupting the toxic inflammatory cycle using T cells stop proliferation of a-synuclein.

Here is an overview of how the vaccine will work and note at bottom of the page, they have a link to a more detailed explanation with graphics on how it will specifically work in PD brains.

http://www.ibridgenetwork.org/nebras...ccine-strategy

brochure with more detail:

http://unemed.atticdev.ist.unomaha.e...0000037M1p.pdf

Affiris already has a head start, can this honestly turn into another Duodopa situation where PWP in Europe will reap the benefits while we suffer and progress for at least 10 more years under the ridiculous red tape of the FDA?

Can vaccines be approved any faster? it does raise some feelings of cart before the horse - is it a concern that we are tampering with something we don't know the function of in the first place?