Ann Arbor-based Adeona Pharmaceuticals Inc. (NYSE Amex: AEN) announced Thursday that it has expanded its pipeline of proprietary zinc-based therapies to include a planned Phase IIb clinical trial of patients suffering from amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease.

Preparations are under way to evaluate the safety and efficacy of the company’s proprietary drug candidates, AEN-100, a gastroretentive, sustained-release zinc-based tablet, and AEN-200, a copper tablet, in a multi-center, double-blind, placebo-controlled clinical trial in ALS patients intended to be conducted under an Investigational New Drug application.

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Adeona will provide the study medications and fund the clinical trial, which will be conducted by the neurology team at the PNA Center for Neurological Research in Phoenix, Ariz., in collaboration with The Institute for EthnoMedicine in Jackson, Wyo.

Preparation of the planned Phase IIb clinical protocol is currently ongoing for submission to the Food & Drug Administration as an addition to a current IND application. Efforts are also under way for the manufacturing of clinical trial medications and protocol review by an Institutional Review Board. The multi-center trial is intended to take place at up to six major ALS centers in the United States. It is anticipated that the trial will enroll 60 ALS patients, who will continue on Rilutek (riluzole) as the standard of care treatment. The patients will be randomized into treatment and matching placebo groups and will receive clinical trial medications for 12 months with periodic monitoring. The treatment group will receive Adeona’s proprietary drug candidates – AEN-100, a zinc-based tablet, and AEN-200, a copper tablet.

The planned co-primary endpoints are determining the safety of AEN-100 (elemental zinc) at 150 mg (two 75mg tablets) given to patients once daily with ALS by assessing adverse events and measuring zinc and copper levels every three months; and determining the efficacy of AEN-100 by assessing the rate of disease progression as measured by the ALSFRS-R, a revised ALS functional rating scale that incorporates assessments of respiratory function.

The planned secondary endpoints are: measuring levels of beta-methylamino-L-alanine (BMAA) in blood and urine to determine if there is a decline in these levels over the course of treatment; following disease progression as measured by Forced Vital Capacity, a measurement of lung function that has been shown to correlate with disease survival; and  following progression of muscle weakness through quantitative strength measurements using hand-held dynamometry.

Currently the clinical investigators at the PNA Center for Neurological Research are conducting a Phase I/II open label study of zinc therapy in ALS patients to determine the safety of zinc in conjunction with low doses of copper. To date, no safety issues related to zinc therapy have been observed in the ALS patients.

The clinical investigators at the PNA Center for Neurological Research cite multiple lines of scientific research that suggest a potential benefit of zinc therapy for ALS patients.

During the 1950s, an epidemic of ALS was discovered on the island of Guam and the Trust Territories of the Pacific that revealed a form of ALS that was 100 times more prevalent than in the rest of the world.

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Research on this cluster of ALS cases linked the neurological disease to the neurotoxin BMAA, a non-essential amino acid produced by cyanobacterium and found in large concentrations in food consumed by the people on Guam. Subsequent to the observations of a cluster of ALS cases on Guam, several groups have identified high concentrations of BMAA in the brain tissues of patients from North America and Europe with neurodegenerative diseases such as ALS.

It has been demonstrated that BMAA binds strongly to transition metal ions such as zinc, copper, and nitrogen. If BMAA crosses into the brain and enters a compartment in which glutamate is bound to zinc, the glutamate/zinc complex separates and the BMAA binds with the zinc, leaving high levels of unbound glutamate. These elevated levels of unbound glutamate are believed to be highly neurotoxic in ALS patients. Zinc is thought to serve as an endogenous antioxidant in the central nervous system and helps protect the blood-brain barrier against oxidative stress and may prevent the neurotoxin, BMAA, from crossing into the brain.

The use of zinc therapy for ALS patients is further supported in animal models of ALS. Approximately 2 percent of ALS diagnoses are associated with a mutation in the superoxide dismutase (SOD1) gene. In ALS mutant SOD1 animal models, zinc supplementation has been shown to delay death.

Genetic mutations affecting the ability of a protein known as copper/zinc superoxide dismutase (SOD1) to properly bind zinc are associated with the familial form of ALS, which shares many of the same features as the more prevalent sporadic form of ALS.

Zinc is an important modifier of glutamate toxicity, a neurotransmitter linked to cell death in ALS patients.

“Our goal at the PNA Center for Neurological Research is to improve the quality of life of patients with neurological diseases, such as ALS,” said Todd D. Levine, M.D., President of PNA Center for Neurological Research, Assistant Clinical Professor at the University of Arizona, Co-Director of the Banner Samaritan ALS Center in Phoenix, Arizona and Lead Principal Investigator of the planned clinical trial. “As observed in other central nervous system diseases, the biological availability of zinc is impaired in ALS patients. We hypothesize that by giving high doses of zinc to ALS patients, we can decrease the amount of toxicity from unbound glutamate and prevent neurotoxicity. We are pleased to be working with Adeona and utilizing their proprietary zinc-based therapy that has already demonstrated clinical evidence of being very well tolerated by patients with superior bioavailability.”

Added Adeona CEO James S. Kuo, M.D.: “Adeona’s mission is to develop innovative medicines for serious central nervous system diseases. Expanding our pipeline to include ALS, a devastating and fatal neurological disease for which there is a shortfall of treatment options, is an ideal fit with our expertise and business model. Given the body of scientific evidence suggesting a therapeutic role for zinc in ALS, we look forward to the start of dosing ALS patients in this Phase IIb clinical trial to be conducted under an IND. We are pleased to be working with the dedicated neurologists at Phoenix Neurological Associates.”

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ALS is a devastating progressive neurodegenerative disease that affects the nerve cells in the brain and the spinal cord in people of all ages and both sexes. It is estimated that as many as 30,000 Americans may have the disease at any given time. The progressive degeneration of the motor neurons in ALS eventually leads to the death of the patient. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. When motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed. While non-invasive ventilation and gastrostomy tubes prolong life by 6-12 months, the average lifespan from time of symptom onset is 2 to 5 years. Currently, Rilutek is the only FDA-approved drug for ALS. Rilutek is an NMDA receptor antagonist and has been shown to prolong life in patients with ALS by 3 months. Presently, there is no cure for ALS, nor is there a known cause. For more information on ALS, please visit the ALS Association website at www.alsa.org.