Providing resources and ideas for therapies and medical developments for Parkinson's disease:
Parkinson’s disease motor symptoms are caused by degeneration of dopamine producing neurons in the Substantia Nigra Pars Compacta located in the brain stem on both the left and right sides of the brain and extend to the Caudate Putamen to provide muscle motor control. Recovery and reversal of Parkinson’s disease symptoms will require the protection, restoration and regeneration of these motor neurons. Although as many as 80% of these neurons become ineffective in a Parkinson's patient, research has shown that 70% are still alive, they just are not functioning. Research is being done on growth factors which stimulate intracellular signaling to promote restoration, growth and synapse formation. Of particular interest are restorative therapies to stimulate regrowth and branching of dopamine axons into the caudate putamen.
One simple and natural method to generate neurotrophic factors and enhance neuroplasticity is to exercise. Experiments delivering Glial Cell Line-derived Neurotrophic Factor (GDNF) directly to the brain required complicated stereotactic surgery because GDNF (and many neurotrophic factors) are unable to cross the blood brain barrier. Neurotrophic factors are also hindered by poor diffusion into tissue and thus the inability to to reach a sufficient number of dopamine neurons to be an effective therapy. Exercise is much safer, simpler and effective promoter of GDNF. See our discussion of physical therapy and exercise to help Parkinson's patients
One effort to develop a GDNF therapy to regenerate neurons is being lead by the National Institute of Neurological Disorders and Stroke (NINDS) and is in a five year phase 1 trail (NCT01621581).
Lion’s mane mushrooms (Hericium erinaceus) have been the subject of research for their apparent ability to help repair nerve damage by inducing the biosynthesis of nerve growth factors (NGF). This is an important distinction to the direct use of NGF which are not able to cross the brain blood barrier due to their physical size. Hericium erinaceus has been used as an herbal medicine in East Asian countries and goes by the name Yamabushitake in Japanese, Houtougu (monkey head) in Chinese, and Lion’s Mane in English. It is believed that its active ingredient is Erinacine A which has antioxidant, anti-aging, antimicrobial, hypolipidemic (cholesterol-lowering), anticancer, immune modulation and neuro-protective properties. The therapeutic potential is being applied to those with peripheral neuropathy, Alzheimer's and Parkinson's. Some results of experiments on mice induced with Parkinson's disease by injecting them with MPTP, showed that treatment with Hericium erinaceus decreased the loss of dopaminergic neurons and a decrease in oxidative stress-induced apoptosis (cell death). Of course animal studies are not conclusive of human efficacy. Lion’s mane mushrooms are available as a dried and ground supplement.References:
Lion’s mane mushrooms are an edible mushroom characterized by its dangling spines.
Lion’s mane mushroom extract and mushroom supplements
Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is a drug which has been found to have general nootropic (improve cognitive function) and neuro-protective properties and specifically for Parkinson's patients it has been found to have an effect on alpha-synuclein oligomerization and fibrillation, the mechanism of Parkinson's motor neuron degeneration. Noopept is a nootropic peptide that was developed in Russia to treat age-related cognitive decline and prescribed primarily for the treatment of Alzheimer’s disease, dementia, and other age related cognitive decline. Noopept improves memory by increasing Brain Derived Neurotrophic Factors (BDNF) and Nerve Growth Factors (NGF) found to generate fresh neurons as well as preserving damaged neurons in the Hippocampus. Noopept can be taken orally in powder, tablet or liquid form and can pass through the Blood-Brain Barrier (BBB). Typical doses are 10 – 30 mg per day depending on weight.Dosage per day:
(eg 10 mg, 3 times a day for a 200 lbs person).
A similar nootropic and cholinergics drug is Piracetam. Both Noopept and Piracetam are unregulated by the FDA.
Farnesol is a natural compound found in berries, fruits and herbs and capable of inhibiting a protein called PARIS which sabotages the neuro-protective properties of another protein, PGC-1 alpha. Without the protection of PGC-1 alpha, dopamine neurons become dysfunctional and die off, leading to the symptoms of Parkinson's disease. Research at Johns Hopkins University has found farnesol to both significantly prevent the loss of dopamine neurons and reverse motor deficits in mice, indicating its promise as a potential treatment for Parkinson's disease. Mice with Parkinson's which were fed the farnesol supplemented diet, had twice as many healthy dopamine neurons and 55% more PGC-1 alpha in their brains than those not fed the supplemented diet.
While farnesol is used as a flavoring and aromatic by the food and tobacco industry, it is not yet available as a supplement or drug. Also, dosages for human use have not yet been determined.Foods and plants containing farnesol include:
This alkaloid derived from the central African root bark of the Tabernanthe iboga shrub has been found to increase levels of glial cell line-derived neurotrophic factor (GDNF) and thus has the ability to influence neurogenesis giving it potential as a therapy for neurodegenerative diseases such as Parkinson's disease. GDNF can cause sprouting of dopaminergic neuron fibers and clinical improvement in animal models of Parkinson’s disease and typically requires brain surgery to administer the compound. Ibogaine is a stimulator of GDNF expression in the central nervous system, and thus a much less risky and less invasive approach compared to surgery.
Ibogaine is classified as a Schedule I substance, which makes it illegal for use or possession in the USA. It is also banned in Australia and many European countries but is legal in Canada, Mexico and New Zealand.
Research on mice has shown that the LINGO-1 protein is found to be elevated in the substantia nigra of Parkinson's patients and that inhibition of LINGO-1 activity was found to be neuro-protective for midbrain dopaminergic (DA) neurons and induced neurite (axon and dendrites) outgrowth. While the research is promising there is no therapy available for human use.