NYC Healthcare News



Adeona enters agreement to begin proprietary zinc-based therapy Phase IIb trial in ALS

April 13, 2016

During the 1950's, 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. 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 (BBB) 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% 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. 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," 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. "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."

"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," said James S. Kuo, M.D., M.B.A., Chief Executive Officer of Adeona. "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."

SOURCE Adeona Pharmaceuticals, Inc.