Can a Protective Interstitial CNS Drug Prevent or Slow the Damage of ALS?
Can a Protective Interstitial CNS Drug Prevent or Slow the Damage of ALS?
Abstracts & Commentary
Sources: Tikka TM, et al. Brain. 2002;125(Pt 4):722-731; Shaw PJ. Brain. 2002;125(Pt 4):693-694.
Motor neuron diseases (MND) in these 2 articles are the same as lower motor neurons (LMN) in amyotrophic lateral sclerosis (ALS) in the United States. Both above reports emphasize that LMN deterioration usually begins and develops in particular body areas such as the distal area of one upper or lower limb or of the lower cranial nerves. It then advances gradually and steadily, part by part in disintegrating LMN in ipsi-or contra-neuromuscular zones. Thus far, no medication has been able to seriously slow down or halt this most vicious illness which usually strikes middle adult or lower elderly patients (some familial cases, however, can start as young as the late teens). Approximately 10% of ALS cases are familial and some 20% of those show indications in the CuZn-superoxide dismutase (CuZn-SOD) gene. Many cases reflect dysfunctional glutamate homeostasis. Recent studies also have identified glutamate as playing a large, abnormal part of genetic somatomotor dysfunction in all somatic motor activity. Riluzole acts as a modest glutamate release/inhibitor and appears to be the only treatment to have even a modest protective effect in the early days of ALS.
Commentary
Shaw clearly emphasizes in her editorial that Tikka and colleagues took the clear CSF of each of 3 different ALS patients and added each sample to a cell culture of a neurological disease different from ALS. Each of the 3 functional CSF cultures gave way to produce apoptotic degeneration of both neurons and microglia. The CSF samples from the other non-MND neurological disorders did not have that lethal touch. When N-methyl-D-asparate (NMDA) and AMPA receptor antagonists were applied to the ALS patients, they prevented the microglial damage of ALS. Minocycline also added to the cultures and prevented death to either assault.
Through a somewhat complicated set of experiments, Tikka et al conclude that all motor neuron cases are susceptible to cytotoxic action that can be identified by specific testing of CSF. Whether or not minocycline will turn out to be clinically effective remains to be seen. —Fred Plum, Editor, Neurology Alert.
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