AbstractBackgroundSpinal Muscular Atrophy (SMA) is the leading genetic cause of infantile death. It is caused by the loss of functional Survival Motor Neuron 1 (SMN1). There is a nearly identical copy gene, SMN2, but it is unable to rescue from disease due to an alternative splicing event that excises a necessary exon (exon 7) from the majority of SMN2-derived transcripts. While SMNΔ7 protein has severely reduced functionality, the exon 7 sequences may not be specifically required for all activities. Therefore, aminoglycoside antibiotics previously shown to suppress stop codon recognition and promote translation read-through have been examined to increase the length of the SMNΔ7 C-terminus.ResultsHere we demonstrate that subcutaneous-administration of a read-through inducing compound (TC007) to an intermediate SMA model (Smn-/-; SMN2+/+; SMNΔ7) had beneficial effects on muscle fiber size and gross motor function.ConclusionDelivery of the read-through inducing compound TC007 reduces the disease-associated phenotype in SMA mice, however, does not significantly extend survival.

15 Oct 2009·Human Molecular GeneticsQ2 · BIOLOGY

Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model

Q2 · BIOLOGY

Article

Author: Allison D. Ebert ; Cheng-Wei Tom Chang ; Christian L. Lorson ; Virginia B. Mattis ; Marina Y. Fosso

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality and is caused by the loss of a functional SMN1 gene. In humans, there exists a nearly-identical copy gene known as SMN2 that encodes an identical protein as SMN1, but differs by a silent C to T transition within exon 7. This single nucleotide difference produces an alternatively spliced isoform, SMNDelta7, which encodes a rapidly degraded protein. The absence of the short peptide encoded by SMN exon 7 is critical in the disease development process; however, heterologous sequences can partially compensate for the SMN exon 7 peptide in several cellular assays. Consistent with this, aminoglycosides, compounds that can suppress efficient recognition of stop codons, resulted in significantly increased levels of SMN protein in SMA patient fibroblasts. We now examine the potential therapeutic capabilities of a novel aminoglycoside, TC007. In an intermediate SMA model (Smn-/-; SMN2+/+; SMNDelta7), when delivered directly to the central nervous system (CNS), TC007 induces SMN in both the brain and spinal cord, significantly increases lifespan ( approximately 30%) and increases ventral horn cell number, consistent with its ability to increase SMN levels in induced pluripotent stem cell-derived human SMA motor neuron cultures. Collectively, these experiments are the first in vivo examination of therapeutics for SMA designed to induce read-through of the SMNDelta7 stop codon to show increased benefit by direct administration to the CNS.

01 Dec 1994·Fertility and SterilityQ2 · MEDICINE

Inhibition of adhesion reformation in the rabbit model by meclofenamate: an inhibitor of both prostaglandin and leukotriene production

Q2 · MEDICINE

Article

Author: K. Sue Himebaugh ; Jeffrey M. Gauvin ; William W. Hurd ; Kenneth F. Cofer

OBJECTIVETo determine the relative ability of meclofenamate sodium, a water-soluble inhibitor of both prostaglandin and leukotriene synthesis, to inhibit adhesion reformation.DESIGNProspective, randomized study in a rabbit model.INTERVENTIONSLaparotomies were performed on mature New Zealand White rabbits, and each uterine horn was devascularized and traumatized with unipolar electrocautery. One week later, adhesions were microsurgically lysed. Each rabbit was randomly assigned to one of five different groups, and different solutions or an adhesion barrier were placed into the peritoneal cavities before closure: [1] control, 40 mL of normal saline (n = 8); [2] meclofenamate, 1.75 mg/mL in 40 mL of normal saline (n = 7); [3] Hyskon, 40 mL of 32% dextran-70 (n = 6); [4] meclofenamate 1.75 mg/mL in 40 mL of 32% dextran-70 (n = 6); and [5] TC-7, 40 mL of normal saline plus oxidized regenerated cellulose fabric, Interceed, placed over the site of adhesion lysis (n = 6). Two weeks later, adhesion reformation was scored according to percent involvement of each uterine horn (0 to 4), and adhesion density (0 to 1) and compared using a one-factor analysis of variance.RESULTSAdhesion reformation was greatest in the control group (mean score +/- SEM, 3.7 +/- 0.4) and was decreased, but not significantly, in the Hyskon group (2.7 +/- 0.4). Compared with the control group, reformation was significantly decreased in the meclofenamate group (2.3 +/- 0.2), the TC-7 group (2.0 +/- 0.5), and the meclofenamate/Hyskon group (1.1 +/- 0.3). This last group was also decreased compared with the meclofenamate and Hyskon groups.CONCLUSIONMeclofenamate significantly inhibits adhesion reformation in the rabbit model, especially when used in combination with a 32% dextran-70 solution.

100 Deals associated with TC007(University of Missouri)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Spinal Muscular Atrophy	Preclinical	United States	University of Missouri	30 Nov 2009

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

TC007(University of Missouri)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation