Methods of treating alzheimer's disease, huntington's disease, autism, or other disorders

An autism-independent technology with applications in the treatment of Alzheimer's, Huntington's, autism and other disorders

Inactive Publication Date: 2014-08-06
NORTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Pharmacology-based therapeutics have

Method used

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  • Methods of treating alzheimer's disease, huntington's disease, autism, or other disorders
  • Methods of treating alzheimer's disease, huntington's disease, autism, or other disorders
  • Methods of treating alzheimer's disease, huntington's disease, autism, or other disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Example 1: USVs of low-grade strains compared to random strains of rats

[0081] The core symptoms of autism (1) deficits in social affect and motivation, 2) communication problems, and 3) high incidence of activity abnormalities, especially repetitive behaviors) can be modeled in animals separately using the following behavioral measures: (1) spending on Decreased time in social contact; (2) reduced proportion of pre-social vocalizations; and (3) intermittent ultrasonic vocalization patterns.

[0082] Adult male Long Evans rats were selectively bred for low or random ratios of play-induced presocial ultrasonic vocalizations (USVs) (ie, frequency-regulated 50-kHZ USVs in response to rough and tumbling play behavior). Conspecific test animals of the same selective breeding strain were used. figure 1 A depicts the mean±SEM time these rats spent in direct social contact. figure 1 B represents the proportion of conspecific play-induced pre-social USVs (frequency-regulat...

Embodiment 2

[0084] Example 2: Effect of GLYX-13 on conspecific play-induced pre-social USVs

[0085] as figure 2 As shown in A, conspecific play-induced presocial USVs (frequency-modulated 50 kHz calls) were determined in juvenile male lower-strain rats pretreated with vehicle (1 mg / ml sterile saline s.c.). figure 2 B shows the results of treatment with GLYX-13 (50 mg / kg s.c.) for 15 min before the start of the test using a within-subject design. Monotonic (i.e. below 7kHz bandwidth) proportions of total homogeneous play-induced USVs such as figure 2 shown in C. n=9 / group. *P<.05 Fisher PLSD 2-tailed causality test. GLYX-13 significantly increased the play-induced proportion of pre-social USVs and significantly decreased the monotonic proportion of total USVs.

[0086] These results show that GLYX-13 can reverse social / emotional communication deficits in lower strains of rats.

Embodiment 3

[0087] Example 3: Altered Gene Expression in Lower Strain Animals

[0088] Alterations in gene expression in two brain regions (the mesial prefrontal cortex and the nucleus accumbens) of animals of lower strains were examined by microarray using the method described above in Burgdorf et al., Neuroscience 168, 769-777 (2010), have been These two regions were shown to be functionally associated with play-induced presocial vocalizations (Burgdorf et al., Behav Brain Res 182, 274-283 (2007).

[0089] The list of genes significantly altered in two brain regions of adult lower-strain animals compared to non-selectively bred adult random-strain animals is shown in image 3middle. There was a statistically significant overlap between human autism-associated genes and genes differentially expressed in lower strains of animals (8 altered autism candidate genes / 101 total altered gene representation vs. 25 / 1108 fragmented groups 3.5-fold enhancement compared to chip set bias; P<.05; c...

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Abstract

The disclosure relates, at least in part, to methods of treating autism in a patient in need thereof by administering an effective amount of a disclosed compound, e.g., a NMDA receptor glycine site partial agonist.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Patent Application US61 / 479,593, filed April 27, 2011, and US Provisional Patent Application US61 / 527,744, filed August 26, 2011, both of which are incorporated herein by reference in their entirety. Background technique [0003] Autism can be characterized by impaired social relationships, communication, and restricted, repetitive, and stereotyped patterns of behavior. Autism is currently considered a developmental disorder and heritable, and is affected by currently unknown environmental aggravations. For example, studies of twins have shown strong reproductive heritability of autism; autism occurs in 60-91% of monozygotic twins compared with 0-10% in dizygotic twins and 0.3% in the general population. [0004] A key challenge in this field is to identify autism candidate genes that are functionally associated with autism and thus can be tracked as therapeutic targets...

Claims

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Application Information

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IPC IPC(8): A61K38/07
CPCA61K38/07A61K31/407A61P3/10A61P9/00A61P25/00A61P25/02A61P25/08A61P25/14A61P25/18A61P25/22A61P25/24A61P25/28A61P25/32A61P25/34A61P25/36A61P27/02A61P27/06A61P29/00
Inventor J·莫斯卡尔
Owner NORTHWEST UNIV
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