Safety Study of High Doses of Zinc in ALS Patients
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to determine the safety of Zinc given at 90mg/d in conjunction
      with 2mg/d of copper in ALS patients.
    

Detailed description: 
      Physicians at Phoenix Neurological Associates (PNA) are looking for individuals diagnosed
      with ALS to participate in an open label phase II safety trial with zinc in conjunction with
      copper, used in combination with Riluzole for treating ALS. This investigator initiated trial
      conducted by Drs. Todd Levine and David Saperstein will help determine if zinc given at high
      doses is safe and tolerated and could possibly slow the progression of ALS.

      Over fifty years ago an epidemic of ALS was discovered on the Island of Guam where a disease
      complex of ALS was found to be one hundred times more prevalent than in the rest of the
      world. Research on ALS in Guam linked ALS, along with Parkinson's Disease and Dementia, with
      a neurotoxin, β-methylamino-L-alanine (BMAA). BMAA is a non-essential amino acid and is
      produced by a cyanobacterium found in large concentrations in the food consumed by the people
      on Guam. Subsequently several groups have identified high concentrations of BMAA in brain
      tissues of patients from North America and Europe with several neurodegenerative diseases
      including ALS, Parkinson's Disease and Alzheimer's Diseases.

      A small proportion of ALS, (about 2%), is associated with a mutation in the superoxide
      dismutase (SOD1) gene. Mice who express this mutant gene exhibit a progressive, ALS-like
      neurodegenerative disease.Since it is known that SOD1 binds zinc, and many of the mutant
      forms of this enzyme associated with ALS show altered zinc binding, zinc may play a key role
      in all pathological processes associated with ALS. Previous studies have shown that in ALS
      mutant G93A SOD transgenic mice, actual zinc supplementation delayed death. Zinc has also
      been thought to serve as an endogenous antioxidant in the central nervous system and help
      protect the BBB against oxidative stress and prevent BMAA from crossing into the brain.

      It has been demonstrated that BMAA binds exceptionally strongly to transition metal ions such
      as zinc, copper, and nitrogen. If BMAA crossed over the permeable BBB, and enters a
      compartment in which glutamate was bound to zinc, then the glutamate/zinc complex would
      dissociate in favor of zinc having a stronger affinity to BMAA. This could lead to higher
      levels of unbound glutamate which is believed to be highly neurotoxic in ALS patients. We
      hypothesize by exposing patients to high levels of zinc, both BMAA and glutamate would be
      kept in a bound complex with zinc, i.e. eliminating competitive binding for zinc, which lead
      to less excitotoxic free glutamate and glutamate toxicity would be reduced.
    

Intervention name(s): Zinc and Copper
Intervention type(s): Drug
Intervention description(s): Optizinc 90 mg/d Copper 1 mg
Intervention MeSH terms: Copper
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ALS treatment; Zinc; Copper; BMAA; ALS