By Max Stendahl – Digital Editor, Boston Business Journal May 11, 2017, 1:25pm EDT
“One of the risks of biotech companies is that sometimes you have a hypothesis, and nature just disagrees with you. That’s what happened here,” said GV’s Krishna Yeshwant.
SynapDx’s mission is to provide laboratory testing services to physicians who evaluate children for developmental disorders with the initial goal of enabling earlier detection of autism.
Autism Spectrum Disorders are currently estimated to affect 1 in 110 children in the United States according to the Centers for Disease Control.
SynapDx was founded by Stanley Lapidus and closed a Series A round of venture funding in May 2010 from North Bridge Venture Partners, Bain Capital Ventures, and General Catalyst Partners.
SynapDx’s corporate headquarters is located in Lexington, Massachusetts.
|ClinicalTrials.gov Identifier: NCT01810341|
|Recruitment Status : Completed|
First Posted : March 13, 2013
Last Update Posted : December 17, 2014
This study will prospectively enroll approximately 880 children, at least 18 months and less than 60 months of age, who have been referred to a pediatric developmental evaluation center. Enrolled children will have blood drawn for RNA gene expression analysis and optionally for metabolite, lipid and DNA analysis and undergo a clinical evaluation to determine the presence or absence of a diagnosis of ASD.
The primary objective of this study is:
– To develop an algorithm to classify blood RNA gene expression patterns to maximize agreement between the classification and a clinical assessment of presence or absence of Autism Spectrum Disorders (ASD).
The secondary objectives of this study are:
- To develop an algorithm to classify plasma metabolite and/or lipid profiles in such a way as to maximize agreement between the classification and a clinical assessment of presence or absence of ASD.
- To prospectively assess the clinical sensitivity and specificity of the plasma metabolite and/or lipid profile classification algorithm in a separate population consisting of children referred to a developmental evaluation clinic for a possible developmental disorder (DD).
- To evaluate clinical sensitivity and specificity of various combinations of gene expression signature, metabolite and/or lipid signatures, and presence of ASD-associated genetic variation detected by chromosomal microarray analysis (CMA) or sequencing protein-coding regions of the genome.
|Condition or disease|
The primary aim of this study is to define a gene expression signature indicative of ASD and to establish its clinical sensitivity and specificity. Clinician diagnosis of ASD will be made using DSM-5 as the reference standard instrument. The widely used diagnostic instrument Autism Diagnostic Observation Schedule (ADOS-2) is a typical component of the clinical assessment for a child diagnosed with ASD and this evaluation will be performed on all study participants. Secondary aims of this study are (1) to define metabolite and lipid signatures indicative of ASD and establish their clinical sensitivity and specificity and (2) to determine clinical sensitivity and specificity of various combinations of gene expression signature, metabolite and/or lipid signatures, and presence of ASD-associated genetic variation detected by CMA and sequencing protein-coding regions of the genome
Analyses: Details of the analysis will be specified in a Statistical Analysis Plan (SAP), which will include procedures for handling outliers, missing data, and differences across sites. The SAP will be reviewed and approved by a committee of Principal Investigators (PIs) before unblinding of the validation set.
Primary analyses: The primary outcomes of the study will be the estimates of the clinical sensitivity and specificity of the SDX-002 test to classify subjects according to DSM-5 ASD diagnosis, with associated 95% confidence intervals. Sensitivity and specificity will be assessed on the Validation Phase population based on agreement with the clinical diagnosis of presence or absence of Autism Spectrum Disorder by DSM-5 (published May 2013).
The gene expression signature will be trained on the 500 subject Development Phase set, using 5-fold cross validation over the results of several machine learning algorithms, including partial least squares, support vector machines, and boosted decision trees. The training procedure will generate estimated ROC curves for each method, as well as confidence intervals for the area under the curve (AUC). The final choice of a machine-learning algorithm will be based on AUC, as well as on the estimated performance at the chosen operating point on the ROC curve. The operating point will be chosen to provide high sensitivity at an acceptable specificity.
Secondary analyses: In the majority of patients enrolled to date, consent was obtained for collection of an optional bio-repository sample. The intended analysis of the bio-repository samples has now been established (see also, secondary objectives listed above). The metabolomic and lipomic signatures will be similarly assessed on the subset of the 500 subjects in the Development Phase set who consent to a bio-repository sample. In addition to the gene expression signature, metabolite and/or lipid signatures and DNA analysis will be combined with the gene expression signature in various configurations and the impact of these additional measures on clinical sensitivity and specificity will be evaluated. If these additional metabolomic/lipomic signatures and/or DNA analyses improve test performance, these elements may be included in the SDX-002 assay.
Sensitivity and specificity the final SDX-002 assay will also be assessed among subpopulations using demographic information and the results of developmental testing. There are likely to be few subjects in many of these subpopulations and caution will be used in interpreting the results. Planned subpopulation analyses include gender, age, ethnicity, ASD DSM-IV-TR diagnostic subcategory, DSM-5 ASD severity level (social communication and restricted interests/repetitive behaviors) and ADOS-2 scores.Study DesignGo to
|Study Type :||Observational|
|Estimated Enrollment :||880 participants|
|Official Title:||SynapDx Autism Spectrum Disorder Gene Expression Analysis Study|
|Study Start Date :||March 2013|
|Actual Primary Completion Date :||July 2014|
|Actual Study Completion Date :||December 2014|
More With SynapDx
Autistic people have fought the inclusion of ABA in therapy for us since before Autism Speaks, and other non-Autistic-led autism organizations, started lobbying legislation to get it covered by insurances and Medicaid.
ABA is a myth originally sold to parents that it would keep their Autistic child out of an institution. Today, parents are told that with early intervention therapy their child will either be less Autistic or no longer Autistic by elementary school, and can be mainstreamed in typical education classes. ABA is very expensive to pay out of pocket. Essentially, Autism Speaks has justified the big price tag up front will offset the overall burden on resources for an Autistic’s lifetime. The recommendation for this therapy is 40 hours a week for children and toddlers.
The original study that showed the success rate of ABA to be at 50% has never been replicated. In fact, the study of ABA by United States Department of Defense was denounced as a failure. Not just once, but multiple times. Simply stated: ABA doesn’t work. In study after repeated study: ABA (conversion therapy) doesn’t work.
What more recent studies do show: Autistics who experienced ABA therapy are at high risk to develop PTSD and other lifelong trauma-related conditions. Historically, the autism organizations promoting ABA as a cure or solution have silenced Autistic advocates’ opposition. ABA is also known as gay conversion therapy.
The ‘cure’ for Autistics not born yet is the prevention of birth.
The ‘cure’ is a choice to terminate a pregnancy based on ‘autism risk.’ The cure is abortion. This is the same ‘cure’ society has for Down Syndrome.
This is eugenics 2021. Instead of killing Autistics and disabled children in gas chambers or ‘mercy killings’ like in Aktion T4, it’ll happen at the doctor’s office, quietly, one Autistic baby at a time. Different approaches yes, but still eugenics and the extinction of an entire minority group of people.
Fact: You can’t cure Autistics from being Autistic.
Fact: You can’t recover an Autistic from being Autistic.
Fact: You can groom an Autistic to mask and hide their traits. Somewhat. … however, this comes at the expense of the Autistic child, promotes Autistic Burnout (this should not be confused with typical burnout, Autistic Burnout can kill Autistics), and places the Autistic child at high risk for PTSD and other lifelong trauma-related conditions.
[Note: Autism is NOT a disease, but a neurodevelopmental difference and disability.]
Fact: Vaccines Do Not Cause Autism.