G93AGlycine-93 to Alanine
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The objectives of the studies were to determine whether targeting of the hypothalmo-pituitary-adrenal axis at a specific site using AIMSPRO, the novel multi-protein-peptide conjugate complex, currently in clinical development, could elicit multiple measurable efficacy traits in the G93A SOD1 murine model.
used for genotyping the hMLH1 G93A polymorphism are shown in Table 1.
The results obtained for 196 genomic DNA samples from patients with hematologic malignancies analyzed for the G93A locus are shown in Fig.
In study one, G93A mice were dosed with 5mg/kg AEOL 10150 via intraperitoneal (IP) administration on day one of symptom onset, followed by a daily maintenance dose of 2.
With respect to overall motor activity of the G93A mice, the authors noted that there was a "marked slowing in the rate of disease progression, as well as the absence of specific deficits in the AEOL 10150-treated mice.
Crow's refinement of the transgenic G93A mouse model by treatment at symptom onset is a significant advancement in the tools of drug development for ALS and other neurodegenerative diseases," stated Clayton I.
The unprecedented effort to screen drugs in the mutant G93A SOD1 mouse follows a 2002 study in which ALSA partnered with The National Institute of Neurological Disorders and Stroke (NINDS) to screen a set of over 1000 FDA-approved compounds, termed the NINDS collection, in neurodegeneration assays (models).
Embryonic motor neurons isolated from control and transgenic mice expressing G93A, G85R or G37R SOD1 grown in culture are not differentially sensitive to excessive glutamate stimulation (known to be toxic to motor neurons) or trophic factor withdrawal.