PdCure.org

  Providing resources and ideas for cures for Parkinson's disease:

 

New ideas to approach a cure for Parkinson's Disease:

The primary approach to treating Parkinson's disease is to prescribe drugs to treat Parkinson's symptoms, primarily tremors. There are no medical solutions to halt the progress of Parkinson's disease, nor is there a solution to reverse the damage done by Parkinson's disease. This website covers probiotics, unsafe environment avoidance or mitigation (eg mold, toxins), dieting for autophagy and exercise & physical therapy which are thought to help Parkinson's patients, but are not cures.

The cause of Parkinson's is the migration of a mis-folded alpha-synuclein protein which enters neuron cells and can't be expelled. The neuron cell eventually accumulates too much alpha-synuclein protein and burst and dies leaving behind "Lewy Bodies" as waste by-product. By the time Parkinson's is diagnosed, it is believed that 70% of the neurons in the substantia nigra have been killed.

It is belived that the source or entry point into the body of the mis-folded alpha-synuclein protein is the gut which then migrates along the vegus nerve to the base of the brain (ref Johns Hopkins research).

Research and drug trials are taking the following approach to the problem:
  • Re-purpose existing drugs (eg diabetes ant-inflammatory drugs) to see if there is any efficacy (a shot in the dark by pharma to expand the market for their existing drugs).
    See drugs in trials targeting inflammation
  • Development of drugs to boost the immune system to target mis-folded alpha-synuclein to halt the migration of mis-folded alpha-synuclein from neuron to neuron (immunotherapies have been very effective in fighting cancer).
    See drugs in trials targeting Alpha-synuclein
  • Target alpha-synuclein in the gut (doesn't address alpha-synuclein in the substantia nigra, migrating from cell to cell, causing neuron death).
  • Target alpha-synuclein migration from cell to cell. Focus on transmembrane receptors which allow a cell membrane to allow alpha-synuclein to pass into the neuron cell (works like a lock in a door, admitting only proteins with the right "key"). Investigation of antibodies that block LAG3 protein.
    Also see John Hopkins research to "Cut Parkinson's Disease Off at the Pass"
  • Development of drugs to target the bad behaviour of LRRK2 genetic mutations and the mis-folding of alpha-synuclein.
    See drugs in trials targeting LRRK2
  • Target proteins defined by genetic links: Genes are responsible for the blueprint of protein construction. Some genetic defects and the defective proteins they enable have been identified as culprits in the development of Parkinson's. The proper versions of the proteins are being targeted as potential cures to halt progression (eg PINK1/PARIS/PGC-1alpha).
    Also see Johns Hopkins Team Explores Paris; Finds A Key To Parkinson's
  • Cell death and the PARP enzyme: injury, strokes, Alzheimer's disease and Parkinson's disease share a common brain cell death mechanism. They all involve the PARP enzyme, the mitochondrial apoptosis-inducing factor (AIF) protein and macrophage migration inhibitory factor (MIF). A treatment is being investigated which blocks MIF action to protect neuron cells from death.
    Also see rain Cell "Executioner" Identified
  • Target Lewy bodies and plaque clean-up (damage is already done, neurons are dead, not sure how this helps).
Also see Parkinson's Disease Drugs in Trials for a list of experimental drug approaches.

New Ideas:

There seems to be approaches which are not being considered:

Re-fold and correct mis-folded alpha-synuclein:

The following approach relies on a technology known as Pharmacoperone or Pharmacological chaperone. This technology uses a protein that enters cells and serves as a "molecular scaffold" to promote correct folding of otherwise-misfolded mutant proteins within the cell. This requires knowing the protein fold of mis-folded and correctly folded alpha-synuclein and then developing the Pharmacoperone protein.

Protein Folding: The University of Washington is the leader in protein design and protein folding. They have released many software packages for the study of this subject:
  • FoldIt: a gamified approach to involve humans and computational chemistry

Once the protein to provide the "molecular scaffold" has been defined, traditional biotech science can be utilized to generate the protein as a drug. This requires DNA gene editing to define the amino acid sequencing to produce the the protein which provides the proper "molecular scaffold". The edited DNA is then inserted into a cell used as the molecular factory to synthesize the "molecular scaffold" protein. The next step is to provide a delivery mechanism to deliver this protein to the affected area (substantia nigra) to fix the mis-folded alpha-synucleins which are destroying neurons. This is hoped to halt the progression of Parkinson's. To make this approach optimal, it would have to be administered as soon as Parkinson's is detected necessitating new methods of early detection. I do not know of any research taking this approach but feel that it is an idea which can be improved and built upon.

Ideas of Others:

  • A case for chondroitinase: how we may be able to reduce some of those inhibitory factors in neuron stem cell transplantation
Thinking - Creative Commons