Dr Lazar (Gerald) Freidman shared with us his presentation from the recent Chemed conference in Medical Ethics in Toronto Canada

In his presentation Dr Friedman discusses current issues in ASD – the clinical features of the disorder and its epidemiology (the study of how often diseases occur in different groups of people and why) and clinical features of ASD.

He mentions the current methods of diagnosis- the challenges faced in the process and the limitations the methods have. Lastly – Dr Friedman reviews a new direction in autism diagnostics based on biomarkers and reviews the current Cell El diagnostic study of ASD biomarkers.

To view the full lecture – please click here. You can view the lecture for free, however you will be asked to submit your email address and they will then mail you a link to Dr. Friedman’s lecture.

To view a more detailed synopsis of the presentation/our interview with Dr Friedman, keep reading.

Dr. Gerald Friedman is a consultant pediatrician at the Autism clinic of the Children Treatment Network (CTN) in Toronto. He is the principal site investigator for the Cell El Autism research study at CTN. He has a practice focused on Developmental Pediatrics and Pediatric Neurology.

Dr. Friedman is on the Faculty at the University of Toronto in the Department of Pediatrics. Dr. Friedman is the former Chief of Pediatrics and Medical Director of the Woman & Child Program at Mackenzie Health. He completed his pediatric residency and pediatric neurology training at the Hospital for Sick Children in Toronto. Dr. Friedman is a member of Cell-El’s Advisory Board.

Dr. Gerald Friedman answers questions about Autism Spectrum Disorder (ASD). He explains the epidemiology, clinical spectrum, diagnostic challenges and how the discovery of ASD related biomarkers can make a difference.

Why is ASD more prevalent today than it was before?

In the last two decades, the prevalence of autism has risen higher and higher. This is not only a North American problem, a publication from January 2024 showed that the prevalence is rising in Israel as well as globally. This affects a lot of people in many ways. So why is the number going up? There are many different theories as to why the prevalence is going up so much.

Forty years ago, autism was classified as a severe disorder, mild cases weren’t diagnosed. It was understood that not everyone is a clone and fits in a box. The majority of the cases being diagnosed today are the milder cases.

This is happening in many fields in addition to autism such as anxiety, ADHD, OCD. Once you open the diagnostic parameters to be more inclusive, by definition you will have a rise in prevalence. So we don’t have to worry that the world is falling apart, it’s just that what we are calling autism today is different and more inclusive than a few decades ago and that’s why there are more cases. This rise is fueled by public awareness, media and social networking. It is also important to note that an specific medical diagnosis will open doors and allow one to receive proper treatment and services as they need.

What is the clinical spectrum of autism? Do we need to adjust the terms of the clinical spectrum?

The clinical spectrum is often misunderstood. Many people think of it as a spectrum of mild/moderate/severe cases of autism and it is more complicated than that.

There are different parameters for ASD, and within each one there is a spectrum. For example we can look at different behaviors. It can go from nonverbal aggressiveness, lashing out, to just odd, atypical, and quirky behavior. If we look at skills, you will find children reading the newspaper at 3-4 years old, yet they can’t  communicate properly and instead of saying hello, they will say “2,6,4”. They have that savant type of skills, doing math and things in their head. A lot of these individuals have a high IQ and are highly intelligent but it comes at a price of social integration.

How would you decide what is mild? take a person who is verbal, speaks, has a degree, but they go from job to job every 2 months and they can’t sustain a relationship. Would you call that  mild, moderate or severe autism? Compared to someone nonverbal in a group home, it’s mild, but the family doesn’t see it as mild. Because of all these issues, the different spectrums and the ambiguity of the different levels in the spectrum, I think that the terms of the clinical spectrum will need to be readjusted in the next few years.

What are the main issues with the diagnostics?

One of the main issues today is that we need a medical diagnosis, which is incredibly time consuming. A study in the USA shows that individuals wait between 4 – 12 months to get a diagnosis. Time is crucial, in this case time = brain cells, and waiting so much time is not good. That is why biomarkers are such an important topic when it comes to diagnosing ASD.

Biomarkers- what are biomarkers and why are they important?

When we see a patient – we see all types of behaviors and symptoms but we always see what the explanation is of what we are looking at. There are kids that come into the clinic and you could look into the waiting room and already make a diagnosis. But to make a more accurate diagnosis we need more information- ideally, objective information. For example- information from the blood/ serum – which we call ‘biomarkers’. Biomarkers are used in many areas of diagnosis where we want to better understand what is going on underneath – like in Alzheimers with TAU markers.

If we were to identify the biomarkers needed for the accurate diagnosis of autism, we may be able to identify which children are at risk- even before they show outward symptoms. We can take a high risk population – a sibling, a cousin, family history – and check them for these biomarkers. We could possibly identify them at 12 or even 9 months of age which we cannot really do now –  and provide early intervention.

How could biomarkers help in treatment?

The biomarkers may not only distinguish a child developing ASD from a neurotypical child, they may be able to help us distinguish subgroups of patients. Which patient needs which intervention and which patient may respond best to a certain treatment.

Biomarkers are not only in the blood- there are many researchers today working on identifying different types of biomarkers. There are researchers in the US and Canada working on behavioral biomarkers even – studying eye movement, watching videos of babies at 1 year of age and tracking to see if they have the eye contact that they need to have. There are also genetic biomarkers – which is an exciting topic all of its own in terms of markers. A child may have a deletion of genetic information but that isn’t always causative but rather just an association with the condition. Fragile X and tuberous sclerosis are two conditions with genetic mutations which are associated with autistic behavior and share a comorbidity with ASD. 

Another area of biomarkers researchers are exploring in ASD is metabolics: Researchers have found some individuals with ASD to present with mitochondrial disorders, methylation redox issues and other metabolic challenges. Neuroimaging like MRI was thought that it would be helpful for objective diagnostics but today we only do MRIs when the child also presents with seizures. You need a higher level of imaging to be able to use this as an ASD biomarker – researchers are working on this now in Boston.

So there are many researchers working in the field of ASD biomarkers – we at Cell El are not the only ones.

What is the Cell- El ASD biomarker study all about?

Our study is looking at the immune response and how that could possibly be a biomarker for ASD. Besides taking a family history – there have been many studies over several decades which show an association between immune markers and autism. However this association has not yet been determined clearly enough to be used for ASD diagnostics. For example- auto-antibodies in the brain have been associated with ASD as well as certain humoral immunity markers.

Maternal immunology is interesting too: For example, when they looked at mothers who had more infections during their pregnancy – doesn’t matter what type of infection – any infection- there was a correlation between the number of infections and the number of ASD cases. There is something that occurs to the blood brain barrier- this is possibly part of the mechanism of developing ASD which is not yet understood.

Epigenetics is gene expression which is influenced by the environment. There are genes that are present in an individual but they get ‘turned on’ or ‘turned off’ and make different things happen depending on environmental stimuli. This could be what we are seeing across the blood brain barrier.

In our study at Cell-El we hypothesized that if we can create a diagnostic tool for ASD which is based on biomarkers, we can use that information to also possibly understand the root cause of ASD. Knowing the biomarkers which indicate the root cause could help guide appropriate treatment. It can also help differentiate ASD from disorders with similar comorbidity (like fragile x and tuberous sclerosis as we described earlier) as many neurodevelopmental disorders share.

Cell-El’s Research Article

Our paper – published in February 2023 describes the following study which we performed: Blood was collected from about 200 participants – half of which were diagnosed with ASD and half were typically developing (TD). The study PI is Professor Avraham Steinberg of Shaare Tzedek Medical Center in Jerusalem. Participants were from several locations including from Toronto, Canada. It was important to determine and exclude children with recent illness as not to confuse the data regarding the immune system. If we are looking at dysfunction in the immune response in ASD and a kid was recently ill – we may see that immune response in his biomarkers and that would be confusing and color the data. Our study focused on males predominantly as autism is much more prevalent in males than in females.

We are aiming to create an immunoassay (blood test) based on the markers we identified to be unique to ASD. The first 6 markers we list have already been identified in autism in other research papers. The problem is that it’s not a binary test, having 1 or even 6 markers doesn’t help and isn’t enough for diagnosis. So what we found in our study, with the help of statistical analysis are 6 more markers – so we now have a list of 12 biomarkers for ASD. The question is now with these 12 biomarkers, can you then find a child with ASD? Our sensitivity (identify the positive)was 87% and our specificity (identify the negative)  77%. Is that sufficient? The argument goes that it’s not the worst thing to have more false positives, so more kids get some extra therapy – that is not the end of the world.

Are we there yet?

No – this is the beginning of a research idea that will hopefully become a diagnostic kit. We want to collect more data on more children as well as add new study groups like infant siblings to kids with ASD who are at high risk. How the test will be used is also something we have to think about – will it be used only for high risk siblings of children with ASD, those with a family history? Or should it be used by pediatricians for all children at 18 months of age where there is a delay.

For the full presentation, click here.