Ann Arbor Pharma Firm Testing Zinc For Alzheimer's Treatment

Ann Arbor-based Adeona Pharmaceuticals Inc. (AMEX: AEN) Monday announced the completion of 50 percnet enrollment in Part 2 of its clinical study, "A Prospective, Randomized, Double Blind Trial of a Novel Oral Zinc Cysteine Preparation in Alzheimer's Disease (CopperProof-2)."

The CopperProof-2 study represents the first controlled clinical study of oral zinc cysteine for the dietary management of Alzheimer's disease and mild cognitive impairment.

Part 2 of the CopperProof-2 study is designed as a 60-subject comparator study. Subjects are randomized on a 50:50 basis to receive either Zinthionein ZC or matching placebo. After 3 and 6 months on clinical trial material, serum measurements of zinc and copper are taken, and any changes in cognitive function using standard clinical tests used in Alzheimer's disease and mild cognitive impairment are recorded.

The completion of 50 percent enrollment follows Adeona's April 14 announcement of positive results from Part 1 of the CopperProof-2 study. Part 1 demonstrated a substantially lower incidence of adverse effects in Alzheimer's disease and mild cognitive impairment subjects (33 percent versus 100 percent) in favor of Zinthionein ZC (containing 150 mg of elemental zinc acetate and 100 mg of cysteine) compared to Galzin (containing either 50 mg or 100 mg of elemental zinc as zinc acetate).
Zinthionein ZC also demonstrated superior serum zinc bioavailability in Alzheimer's disease and mild cognitive impairment subjects compared to both the 50 mg and 100 mg dose levels of Galzin.

"Having pioneered the use of oral zinc therapy in dry age-related macular degeneration, which has now become the standard of care, I believe that Adeona's once-daily, high bioavailability, well-tolerated oral zinc cysteine formulation has the potential to ameliorate the sub-clinical zinc deficiency in Alzheimer's and mild cognitive impairment subjects and substantially grow current markets for oral zinc-based therapies," said David Newsome, M.D., Adeona's senior vice president for research and development.

Added Adeona CEO James S. Kuo, M.D.: "We are pleased to have reached this enrollment milestone on a timely basis and within budget. Along with the recently announced Meda collaboration for flupirtine's development and completion of 50 percent enrollment in the Trimesta multiple sclerosis clinical trial, it represents one of several major transformational changes taking place at the company in the past few months."

Observations by Adeona scientists and other scientists of sub-clinical zinc deficiency in Alzheimer's disease patients plus a body of published literature that chronic elevated copper exposure contributes to the progression of Alzheimer's disease and mild cognitive impairment prompted the present CopperProof-2 clinical study.

Alzheimer's disease can affect the entire brain but it is particularly associated with loss of tissue in the hippocampus, the area in the brain responsible for several functions including short-term memory retention and processing. The hippocampus has one of the highest concentrations of zinc in the brain. Hippocampal zinc is thought to play a role in hundreds of protective enzymes and other systems, including those that detoxify amyloid beta, an abnormally folded peptide that accumulates in aging and is a biomarker for Alzheimer's disease. When cerebrospinal fluid zinc is low, levels of the particularly toxic beta amyloid 42 are elevated.

Hippocampal zinc serves as a neurotransmitter, and also modulates a specific neuroreceptor. If the neuroexcitation goes uncontrolled, there is a derangement of brain tissue function, and possibly neuronal death. By elevating cerebrospinal fluid zinc, the receptor excitation may be better controlled, improving tissue function and thereby acute cognition and tissue survival, as may have been seen in the 1992 study. NMDA-receptor antagonists now available for Alzheimer's, including Namenda and Axura, annually sell an estimated $2.6 billion.

Zinthionein ZC is a once-daily, gastroretentive, sustained-release, oral tablet formulation of zinc and cysteine. Zinc, an essential nutrient, participates as a necessary factor in the activity of over 200 enzymes and the DNA binding capacity of over 400 nuclear regulatory elements. Zinc may also directly participate in antioxidant protection by reducing the susceptibility of sulfhydril groups to damage by oxidative free radicals. Cysteine is an amino acid that has potent anti-oxidant properties and is a necessary component of the copper-zinc-binding protein, metallothionein.

Zinthionein ZC was invented and developed by Adeona scientists to achieve the convenience of once-daily dosing, high oral bioavailability and to minimize gastrointestinal side effects associated with other commercially available, oral zinc products. All of Zinthionein ZC's constituents have GRAS (Generally Regarded as Safe) status. Adeona is developing Zinthionein ZC as a prescription medical food for the dietary management of Alzheimer's disease and mild cognitive impairment. Zinthionein ZC is protected by multiple U.S. and international pending patent applications held by Adeona.

Adeona is a pharmaceutical company developing new medicines for serious central nervous systems diseases. Adeona's primary strategy is to in-license clinical-stage drug candidates that have already demonstrated a certain level of clinical efficacy and develop them to an inflection point in valuation resulting in a significant development and marketing collaboration.

Its other drugs include Trimesta (estriol) is an investigational oral drug for the treatment of relapsing remitting multiple sclerosis, currently in clinical trials, and Effirma (flupirtine), a centrally-acting investigational oral drug for the treatment of fibromyalgia syndrome. Adeona has entered into a potential $17.5 million corporate partnership with Meda AB. As part of the agreement, Meda will assume all future development costs while Adeona is entitled to receive milestone payments and royalties.