Case Number 109051 - Allantoin as non-invasive neuroprotective therapy for Parkinson's disease
Contact: Michael Hansen
Description: Dr. Brian Terpstra and Dr. Caryl Sortwell have discovered that allantoin holds great potential as a non-invasive global neuroprotective therapy for Parkinson's disease.
Parkinson's disease (PD) is a disorder of the brain that leads to shaking (tremors) and difficulty with walking, movement, and coordination. A number of different compounds are being investigated as a treatment, including oral administration of inosine (metabolized to urate), which is currently in Phase II trials (Safety of Urate Elevation in Parkinson’s Disease, SURE-PD). The goal of the SURE-PD trial is to determine whether oral inosine supplementation can safely elevate plasma urate without leading to hyperuricemia and gout. Urate, or uric acid, is believed to be the neuroprotective agent to slow PD progression. However, the efforts of Drs. Terpstra and Sortwell have shown that neither inosine nor urate is the molecule responsible for neuroprotection in a rodent model of Parkinson's disease. Their research instead shows that when the conversion of urate to allantoin is blocked then the neuroprotection associated with inosine administration is similarly blocked. Further, administration of allantoin alone results in the same level of protection against the motor impairment and nigral dopamine neuron loss (neurons lost by PD) normally induced
in the rodent PD model. Lastly, in rats with elevated levels of uric acid no neuroprotection was observed. Compared to uric acid, allantoin: 1) has a greater ability to cross the blood brain barrier and access the brain and 2) will not increase the risk of hyperuricemia and gout. Collectively these findings suggest that allantoin administration is potentially better treatment for PD than inosine.
Allantoin is the end product of purine metabolism in most mammals and is also found in botanical extracts of the comfrey plant. It is a normal component of the human diet and can be found in small amounts in eggs, bananas, peas, bread, yams, wax beans and milk, to name just a few. Plasma allantoin levels are significantly elevated during strenuous exercise. The biological activity of allantoin has rarely been scientifically examined and the compound has been widely touted as a biologically inert. It can be found in a number of existing products including toothpaste, mouthwash, shampoos, lipsticks, anti-acne products, and sun care products. However recently there has been more interest in the pharmaceutical use of the compound. For example the FDA has approved it as topical treatment for wound treatment. Additionally in vitro allantoin has been shown to have intrinsic anti-oxidant properties and has been shown to be as potent as ascorbate in quenching hydroxyl radicals. In the studies at UC, allantoin's effect on NADPH oxidase-1 immunoreactivity (NOX-1ir) neurons in vivo suggest that allantoin can reduce oxidative stress and be able to modify the underlying disease process of Parkinson's disease.
Allantoin has great potential as a treatment for Parkinson's disease because:
- It potentially has a more favorable safety trial and ability to access the brain when compared to oral inosine administration
- Our preclinical evidence in a rodent model of PD suggests that allantoin, not inosine or uric acid, is responsible for the neuroprotective effect
- Our data in NOX-1ir cells suggested that allantoin will reduce oxidative stress and be able to modify the underlying disease process of Parkinson's disease.
- Allantoin is a readily available low cost compound.
The University of Cincinnati has a patent pending in the US (13/265,584) and Europe (EP 10767828), based on PCT application # PCT/US10/32201 entitled "Allantoin Administration for the Treatment of Neurogenerative Disease and Neurotrama."
A copy of Dr. Terpstra's thesis entitled Purine Nucleoside Mediated Neuroprotection in the 6-Hydroxydopamine Rodent Model of Parkinson's Disease is available for review.