Memantine Therapy in Amyotrophic Lateral Sclerosis
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Tau, a protein in the cerebrospinal fluid CSF is believed to be elevated in amyotrophic
      lateral sclerosis (ALS) patients. The investigators believe that Tau is truly a marker of
      increased neuronal death from any disease process. It is been shown that Memantine can
      inhibit and reverse the abnormal hyperphosphorylation of Tau and therefore the investigators
      are looking at the efficacy of Memantine at 10 mg twice a day (BID) to see if disease
      progression correlates with possible changes in Tau in ALS patients based on ALS Functional
      Rating Scale (ALSFRS) scores.
    

Detailed description: 
      We have been very interested in the role of developing a more active anti-excitotoxic
      cocktail for patients with ALS. As part of this interest we have been investigating potential
      markers for disease progression. One of our candidate markers has been the presence of
      elevated levels of TAU in the CSF of patients with ALS. While the presence of Tau was
      originally described as being used for adjunctive diagnostic testing in patients with
      Alzheimer's disease it has become clear that many neurodegenerative diseases possess elevated
      levels of Tau in the CSF. Therefore Tau is truly a marker of increased neuronal death from
      any disease process.

      While levels of Tau have not been studied in depth in ALS, there was one report in 2003 which
      showed that 70% of ALS patients have elevated levels of Tau in their CSF (Sussmuth et al). We
      have also collected a series of 24 patients with clinically definite ALS and found that 22 of
      them had elevated levels of Tau at the time of diagnosis.

      We have been intrigued by the findings that Memantine, an NMDA receptor antagonist, can
      inhibit and reverse the abnormal hyperphosphorylation of Tau which leads to sequestration of
      the normal Tau microtubules as well as microtubule associated protein 1 (MAP-1) and MAP-2.
      Further, Memantine has been shown to block the disassembly of microtubules which follows the
      hyperphosphorylation if Tau (Li et al., 2004).

      We have submitted for presentation to the International Motor Neuron Disease meeting in 2005
      the data on two anecdotal cases of patients with ALS. These two patients were diagnosed with
      ALS on clinical and electrophysiological data and they were found to have elevated levels of
      Tau in their CSF at the time of diagnosis. Both patients were treated with Riluzole, as
      standard therapy, and with Memantine 10 mg BID for 6 months. After 6 months their disease
      course was clearly very slow. A repeat analysis of their CSF showed that levels of Tau had
      returned to normal.
    

Intervention name(s): Memantine
Intervention type(s): Drug
Intervention MeSH terms: Memantine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ALS