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Objective: To examine the potential validity of performance measures and examination-based scales in Friedreich ataxia (FA) by examining their correlation with disease characteristics., Methods: The authors assessed the properties of a candidate clinical outcome measure, the Friedreich Ataxia Rating Scale (FARS), and simple performance measures (9-hole peg test, the timed 25-foot walk, PATA test, and low-contrast letter acuity) in 155 patients with FA from six institutions, and correlated the scores with disease duration, functional disability, activity of daily living scores, age, and shorter GAA repeat length to assess whether these measures capture the severity of neurologic dysfunction in FA., Results: Scores for the FARS and performance measures correlated significantly with functional disability, activities of daily living scores, and disease duration, showing that these measures meet essential criteria for construct validity for measuring the progressive nature of FA. In addition, the FARS and transformed performance measures scores were predicted by age and shorter GAA repeat length in linear regression models accounting for sex and testing site. Correlations between performance measures were moderate in magnitude, suggesting that each test captures separate yet related dimensions of neurologic function in FA and that a composite measure might better predict disease status. Composite measures created using cohort means and standard deviations predicted disease status better than or equal to single performance measures or examination-based measures., Conclusions: The Friedreich Ataxia Rating Scale, performance measures, and performance measure composites provide valid assessments of disease progression in Friedreich ataxia.

Previous attempts to characterize the molecular events that support successful regeneration of axotomized goldfish retinal ganglion cells (RGCs) have led to the discovery of an acidic protein doublet in retina that displays an increased incorporation of 35S-methionine following axotomy, and is known to be axonally transported within the optic nerve. This protein is termed p68/70, reflecting its relative migration in 10% SDS-PAGE. In the present study, an affinity-purified polyclonal antibody to p68/70 (anti-p68/70) was developed and used to assess the species, tissue, and cellular distribution of p68/70. The antibody cross-reacted with homogenates of brain and other tissues from goldfish and closely related fish species. While each goldfish tissue tested expressed p68/70, the levels varied over a 30-fold range, with the highest amounts in brain, egg, and ovary. Immunolabeling of goldfish retina revealed prominent staining of RGC somata, dendrites, and axons. During regeneration, the immunoreactivity of the RGC somata and axons increased dramatically. Intense immunolabeling was also observed in the germinal neuroepithelial cells and rod precursors and in all retinal layers near the peripheral margin, in the region of recently differentiated neurons. In the tectum, the germinal zone was also highly labeled. The elevated expression of p68/70 in each of these areas known to mediate neuronal growth within the goldfish visual system suggests that p68/70 plays a role in axonal growth, regrowth, and possibly in neural development as well.

Kainic acid is supposed to be a specific agonist for a subclass of excitatory glutamate receptors in the vertebrate CNS. An investigation of (2 nM) [3H]kainic acid binding sites in goldfish brain, using quantitative autoradiography, has revealed evidence for two types of kainic acid receptors which differ in sensitivity to glutamic acid. L-Glutamic acid (0.1-1 mM) displaced over 95% of specific [3H]kainic acid binding elsewhere in the brain but only 10-50% in the cerebellum and cerebellar crest. These structures apparently contain [3H]kainic acid binding sites that are extremely insensitive to glutamic acid. The glutamic acid-insensitive [3H]kainic acid binding was not displaced by quisqualic acid, kynurenic acid, alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA), or N-methyl-D-aspartatic acid, but was completely displaced by the kainic acid analogue domoic acid. The data indicate that two types of high affinity binding sites for [3H]kainic acid exist in the goldfish brain: glutamic acid-sensitive and glutamic acid-insensitive. High affinity [3H]kainic acid binding may therefore not always represent binding to subsets of glutamic acid receptors.