In introducing myself to the wider Autism Speaks community, I’d like to start by conveying how thrilled I am to be part of its mission. It’s an exciting time for autism research, especially when it comes to finding new treatments for autism spectrum disorders (ASDs).
Today, we know so much more about the biological mechanisms behind ASDs than we did just a few years ago. We are now poised to make a big leap forward in the development of new medicines and therapies that address the core symptoms. I’m so grateful to be part of an organization that’s leading the charge.
I came to Autism Speaks after almost ten years helping pharmaceutical companies such as GlaxoSmithKline develop clinical trials for safely and effectively testing pediatric drugs for conditions such as bipolar disorder, attention-deficit/ hyperactivity disorder (ADHD), and autism spectrum disorders (ASDs). I have also led clinical programs testing new medicines for chronic diseases such as multiple sclerosis, Alzheimer’s disease, and schizophrenia. These experiences have given me valuable insights into the process behind bringing new medicines through the clinical trial process and into the hands of doctors.
Above all, however, I see myself as a physician. As a child psychiatrist, I care for people who face complicated clinical challenges. Since 1992, I have consulted at a residential treatment facility for children, which I continue to do on a pro bono basis. About a third of the youngsters I care for have ASDs, and I have always loved working with them. Their families are so motivated and passionate, and I enjoy the partnership of working with them, often shoulder to shoulder, to optimize treatment and outcomes.
And I’m most satisfied when we can craft a treatment program that fits a child’s unique needs. I’ll admit, it’s seldom an easy task—given the complexity of ASDs.
As a parent of two children who have experienced significant illnesses, I feel particular empathy for the distress family members feel when treatments fail to provide adequate relief for their loved ones. This inadequacy redoubles my passion for expanding and improving the treatment options available for ASDs. Working with Geri Dawson, Rob Ring and the many passionate scientists at Autism Speaks, I truly believe we will make tremendous progress in the years ahead.
In the last five years, we have greatly advanced our understanding of the underlying biological mechanisms of ASDs. Scientists have not only identified genetic changes associated with autism, but have gone far in understanding how these changes affect the internal workings of brain cells as well as brain development. Such insights open the door to the discovery and development of safe and effective new medicines and other interventions.
Five years from now, I anticipate seeing the many tangible ways that all of us at Autism Speaks—including our families, friends, donors, and volunteers—have helped accelerate the development of better medicines and other tools that truly improve the lives of those on the autism spectrum.
I’ve been following Autism Speaks since its genesis in 2005, and I can’t think of a better team of people for the job. I’m honored to be on the same team with you all. Let’s get started!
This is a post by Autism Speaks’ Assistant Director of Science Communication and Special Projects Leanne Chukoskie, Ph.D.
On Friday, a short post with a link to a clinical trial led by Curemark was highlighted in e-Speaks and on Autism Speaks’ Facebook page. The post generated a many questions and comments, some of which could be addressed with more information about clinical trials in general.
Clinical trials are research tools for studying the health and well-being of people. Clinical trials are not always focused on treatment, but may include studies of better methods for diagnosis, screening or improving quality of life. A description of types of clinical trials is available at an informative website provided by the National Institutes of Health in the FAQ.
In addition to the different types of trials conducted, any clinical trial involving a new drug enters a phased series of tests to assess the safety and efficacy of the drug for a particular population. A Phase I clinical trial is small and establishes safety and appropriate dosage. In Phase II, the trial is expanded to include more subjects so a better estimate of effectiveness and safety can be established. Phase III trials can be conducted after preliminary evidence for the effectiveness and safety of the drug has been favorable. In this phase of study, the effectiveness of the treatment, any potential side effects of the treatment are closely monitored in a larger population. Also this phase typically includes a comparison of the treatment under study with other drugs available for the same condition. A Phase IV clinical trial is called “post-market” research because it is conducted after a drug has been made available for use in the general population. Phase IV studies typically include several thousand participants and help to refine aspects of the treatment’s best usage and ideal treatment candidate.
The Curemark study noted in Friday’s post is a Phase III treatment trial that aims to compare the effectiveness of a compound called CM-AT versus a placebo administered 3x per day for 90 days. This particular trial is “double-blind” meaning that neither the research participants nor the clinical staff administering the treatment know whether a subject is receiving the active compound or a placebo at the time the treatment is given. Double-blinded studies are believed to produce more objective results because the outcomes are not influenced by the subjects’ or clinicians’ expectations about the treatment. Treatment information will be revealed for all subjects when the blind is broken at the end of the study at which point an analysis of the effectiveness of the new treatment versus control can be compared.
The clinicaltrials.gov website lists 219 studies that result in a search for “autism.” A smaller number (110) are seeking volunteers. The treatments being assessed include behavioral therapies, different drug compounds, transcranial magnetic stimulation (TMS) and others from researchers all over the world. 12 of the 219 studies were sponsored by Autism Speaks and nine of those are actively recruiting. We encourage anyone interested in participating in research to seek more information about these studies.
This post is by Leanne Chukoskie, Ph.D. Dr. Chukoskie is the Asst. Director Science Communication and Special Projects at Autism Speaks and Asst. Project Scientist, Institute for Neural Computation, UCSD.
On Friday, the New York Times published a story about a small clinical trial for a drug that ameliorated some of the symptoms of Fragile X Syndrome in some of the participants in the trial. Single-gene disorders, such as Fragile X Syndrome have been instructive in helping us understand the biology of the broader autism spectrum disorders (30% of people with Fragile X have an ASD). The effort described in the New York Times is not singular, but instead an area of active pursuit by many. Here is some history behind the Fragile X drug story and a summary of clinical trials for single-gene causes of ASD.
As noted in the article, the excitement began in 1991 when Steve Warren, Ph.D. (Professor at Emory University and member of Autism Speaks’ Scientific Advisory Committee) and his colleagues identified the gene, FMR1 (fragile X mental retardation 1), that causes Fragile X syndrome. At that point, Warren and others began probing the FMR1 gene pathway to learn its properties and seek a way of correcting the genetic error. The promise of basic research findings was coming to light in Fragile X as early as 2005, with a small workshop organized by Autism Speaks’ staff titled “Promising new leads for autism research: a potential cure for Fragile X” at the International Meeting for Autism Research (IMFAR). At this meeting, Mark Bear, Ph.D. (MIT), Tom Jongens, Ph.D (UPenn) and Bob Wong Ph.D. (SUNY Downstate) presented preliminary findings related to a theory that Fragile X may be caused by over-excitation of synapse (the connections between nerve cells). Proper functioning of the connections between nerve cells requires a balance between excitatory and inhibitory neurotransmitters. It appears that the FMR1 gene was causing this balance to be disrupted so that there was an abundance of the excitatory influences. These researchers found that by damping the activity of a common excitatory neurotransmitter (glutamate) in the brain, many of the symptoms that characterized the animal models of Fragile X disorder disappeared. This theory was referred to as the mGluR theory (for metabatropic Glutamate Receptor) of Fragile X. The drugs that produced improvements in animal models are called mGluR antagonists, because they act by blocking the actions of this glutamate receptor.
Previously, it was believed that one must act early in neurodevelopment to see any improvement in the symptoms of ASD. This basic research was incredibly exciting because several labs were learning that behaviors related to ASD could be ameliorated with drugs in adult animals.
That was several years ago and one might wonder what is taking so long to see useful medicines for these disorders. The process of approving drugs in any field is long and arduous (see blog on translational research and what Autism Speaks has funded). The translation of basic research into viable drugs in clinical trial is often referred to as crossing the “Valley of Death” as so few molecules tested in basic research make it through the process to become useful medicines. That said, several efforts have been made to create drugs for single-gene disorders related to ASD (see 2008 Top 10 story).
In 2008 researchers from the MIND Institute and Rush University reported results from the first trial of mGluR5 antagonists. Results from the small trial indicate that six out of the twelve adults with Fragile X showed improvements in cognitive deficits. This was the first promising news that mGluR drugs were safe and effective in humans and are related to those reported in the New York Times’ article from the Novartis study, which began around the same time.
Seaside Therapeutics is a small biotechnology company founded by Dr. Bear to see if the promising results observed in animals could be offered to families. In 2008, Seaside began enrollment for a clinical trial using a drug that would also dampen glutamate activity but through a different pathway for treating Fragile X. This drug enhanced the activity of a class of receptors that typically suppress glutamate activity. Seaside Therapeutics has expanded this trial to include patients with autism, and has also launched a clinical trial of its own formulation of a specific mGluR5 antagonist for Fragile X. If positive results are found, the next step will be to test these medications on individuals with ASD who do not have Fragile X syndrome.
We’ve been talking a lot about Fragile X, but there is another disorder, called Tuberous Sclerosis Complex (TSC), which offers another path to understanding ASD (approximately 25-50 percent of people with TSC also have an ASD). In 2008, UK researchers conducting a clinical trial with individuals with TSC reported positive outcomes on short-term memory tests of those receiving treatment. Rapamycin, the drug used in this trial and already FDA-approved for cancer, targets the brain signaling pathway that has been found to be disrupted in TSC and that has recently been implicated in autism as well (see 2007 Top 10 story related to TSC and 2008 Top 10 story about translational research).
Basic research in the biological pathways highlighted by genetic studies of Fragile X and TSC was the starting point for these exciting clinical trials. Autism Speaks continues to identify basic research opportunities that may lead to successful treatments as well as support the translation of research on molecules that have shown promise in the lab to medications that help families.