How is ASD treated today in the US and what is the challenge, if any, with this approach?

There are several approaches to treating ASD in the US that include both non-medication therapies, such as behavioral therapy, speech therapy, occupational therapy and physical therapy, alongside medication for co-occurring clinical features such as anxiety, irritability, self-injury and severe tantrums. Non-medication therapy has incredible value in helping children to develop social skills, especially if initiated early in life. While more patients are benefiting from this therapy than a decade ago, there remain significant socio-economic, racial and geographic disparities in access to the services.

There are only two approved FDA treatment for irritability in ASD, but these have tolerability issues and can cause weight gain and tiredness in a significant number of patients. Furthermore, these treatments do not address the core symptoms of ASD, such as challenges with social skills, communication, sensory processing, and restrictive or repetitive behaviors that impair daily function; these are central to defining autism according to the diagnostic manual (DSM-5).

Why do you think personalized medicine holds promise for the treatment of autism?

I am guided by the many trials over the years where I have observed that certain medicines have shown positive responses in addressing the core symptoms in select individuals, but these individuals were never defined as biological subgroups. Many trials have simply failed in the past due to a lack of scientific matchmaking, where we gave the same treatment to broad groups and relied on observer reports for assessing outcomes.

To make progress, we need to recognize ASD as a spectrum disorder with huge variation, or heterogeneity, and be guided by advances in molecular genetics and the biological understanding of the condition. This means linking individuals into biologically defined sub-groups and measuring outcomes that are objective and quantitative. This is the reason for our collaboration with STALICLA; they are pioneering an approach in the commercial setting that we have been advocating for in our academic research as a group.

This approach also resonates with families that they don’t feel heard when their loved ones receive the same ubiquitous approach with no visible progress; because when you know one person with autism, you only know one person with autism.

How do you create patient sub-groups in autism to undertake research within these specific groups?

In recent years, we have seen phenomenal advances in life science tools that allow us to model molecular and cellular signaling and analyze gene and protein expressions from blood samples. When we combine this information with medical history and non-behavioral patient specific features , we can begin to find commonalities and patterns among patients to group them. We can then match biological profiles of the sub-groups in the lab to specific drugs with the aim of correcting any imbalances in cellular activities. If the lab results are positive, we take the investigative treatment into human studies. Since these studies involve specific patient sub-groups that have been biologically defined, we can evaluate fairly quickly if a treatment is having a positive effect or not.

What is the STP1 trial and what does it aim to understand/uncover and how?

STP1 is a proof-of-concept trial investigating a novel combination of compounds, which includes a pan-PDE inhibitor and a modulator of NKCC1, targeting a specifically defined biological dysregulation. This combination has been studied in the lab and will now be investigated in the clinic, in a newly defined biological sub-group of patients with ASD (ASD-Phen1), identified by STALICLA’s proprietary discovery platform DEPI. This is the first time an investigative precision therapeutic is being studied in a biologically defined sub-group of ASD patients where a mutation in a single gene is not responsible for the condition. Our aim is to understand the effect of the combined therapy on quantitative biological outcomes, for example, brain function, memory, eye gaze behavior and others.

What do you hope the future outcome will be when the emphasis is placed on the individual treatment needs of each autism patient?

We are in a new era for NDDs where I think we will see advances similar to those seen in the field of cancer following the discovery of breast cancer genes 25 years ago. Just as there isn’t a single treatment for all-diagnosed breast cancers, there isn’t a single treatment for everyone with ASD. That’s why we progressively aim to develop tailored treatment solutions for as many ASD patients as possible. Watch this space… this is the decade for personalized medicine in autism.