Research Roundup is a monthly newsletter from N of One’s UK-based science writer, Paul Whiteley, PhD. Each month we summarize a few research papers on a variety of topics in one simple, easy-to-read paragraph. It’s our hope that by skimming these each month, you will broaden your knowledge topics currently being explored by researchers and perhaps find information helpful in your journey of navigating a complex autism landscape.
Folinic acid for autism clears another gold-standard experimental hurdle
Yet another gold-standard clinical trial - randomized, double-blind, placebo-controlled - adds further support to the use of folinic acid (leucovorin) in the context of autism spectrum disorder (ASD). Research from India recently observed important significant behavioral changes in some 40 children aged 2-10 years diagnosed with autism using folinic acid compared with a placebo. For those children who also presented with a high-titer of anti-folate receptor autoantibodies, the results following use of folinic acid were particularly marked in terms of the behavioral benefits observed. Importantly too, use of folinic acid for 24 weeks did not produce any strong adverse reactions according to the study authors. Folinic acid works by bypassing an important part of the folate cycle and has previously accumulated some scientific evidence for effects in autism. Folate receptor autoantibodies have similarly been described several times in the research literature as affecting a not insignificant portion of people with autism. Testing and appropriate supplementation is indicated.
N of One has been a proud supporter of Dr. Richard Frye’ research over the years. For more on Folinic acid’s from Dr. Frye, please see our Q&A with Dr. Frye on our website.
Mitochondria and autism: another review, and more reasons to screen
Mitochondria - the ‘powerhouse’ of the cell - already has an important place in autism research and practice. Another recent review provides an overview of just how important this biological machinery might be across multiple biological systems in the context of autism. The review highlights how aside from its powerhouse reputation, mitochondria, particularly in the brain, is involved in various roles ranging from apoptosis (programmed cell death) to synaptic transmission to oxidative stress. Authors conclude that, aside from the huge range of perhaps hitherto unrecognized links that mitochondrial chemistry has to various biological processes, further investigations are warranted on ‘autism-specific’ connections and interventions that may be useful for some.
[Note from J. Rodakis For almost a decade now N of One has strongly advocated for more focus on mitochondrial cell metabolism as one of the most important, yet understudied biological systems at work in autism. Sadly, despite promising work that has led to potential treatments (folinic acid, suramin) the largest autism research organizations have largely ignored this potentially important area. We will not relent]
AI provides clues to how the gut microbiome links to autism
Not a week seemingly goes by without some new discovery linking the trillions of bacteria that call the human gut ‘home’ and the onset and seeming perpetuation of autism for some. How to organize this myriad of information may become easier as various models of artificial intelligence (AI) are brought to bear on this task. New results from Spain show how AI is already making a difference in this area and revealing what specific types of gut bacteria may be important for many. The conclusions: “Outcomes indicate low levels of abundance pertaining to the bacteria Bifidobacterium, Bacteroides, Prevotella, Ruminococcus, Lachnospira and Clostridium.” Authors also went as far to suggest that one or more of these bacterial findings may also be “biomarkers of ASD” particularly in relation to Bifidobacterium. There are certain limitations to such findings; not least that dietary habits are a significant influencing variable on what bacteria predominate in the gut and what this might mean for those infants with autism who also present with limited dietary preferences and feeding habits. But with further work, there are potential patterns to see and act upon.
Full-text: https://www.mdpi.com/2227-9067/11/8/931
School absenteeism and autism: how and why and ideas for what to do
A myriad of potential factors influence school absenteeism in the context of autism but many are ‘modifiable’ and quite easily so. That was one primary message coming from a recent research review from Germany looking at this important issue. Drawing on data from 18 studies, authors observed several important variables that influence such behavior, grouped into ‘school’, ‘individual’ and ‘parents’. They concluded that ‘school factors’ seemed to show the most important overall relationship with absenteeism, covering areas such as bullying, lack of knowledge from educators and poor support systems in place for students with autism. Parental illness and unemployment and an individual student’s intellectual ability and anxiety also exerted an important effect for some too. Making school work for every student is not an impossible goal. Flexible, often small adjustments, linked to individual students' wants and needs can provide just enough impetus that students are able to re-engage with school-based education and all the benefits it brings.
The trajectories of aggressive behavior in autism
“Longitudinal aggression profiles revealed distinct patterns of change over time: 31% displayed persistent aggression, 25% increased, 23% decreased, and 13% never displayed aggression.” So concluded a recent study tracking what happened to aggression and aggressive behaviors from toddlerhood to young adulthood carried out by researchers from the University of California, USA. Drawing on various gold-standard assessment derived longitudinal [tracking over time] data for over 250 young people with ASD, researchers observed various different trajectories relating to aggressive behaviors and how they correlated with core autistic and other symptoms. For many, aggressive behaviors peaked at around 9 years old and declined as maturation into adulthood continued. This was particularly noted for those children with fewer restricted and repetitive behaviors (RRBs) and high non-verbal IQ. For some however, aggression was a continuing feature, and for around a quarter, levels of aggression increased with age. Such work fits well with notions of different developmental trajectories across the very heterogeneous autism spectrum disorder label. It’s never easy to talk about something like aggression in the context of any diagnostic label. Such work however, reveals some important trends that will hopefully spur further conversations about this very human behavior, and what can be done to minimize its effects on the person, their loved ones and their carers.
And finally…
“Fragile X held him back. An experimental drug is helping him break free”
Various news headlines have recently been discussing the potential usefulness of the drug zatolmilast in the context of Fragile X syndrome. Fragile X is caused by mutations in the fragile X messenger ribonucleoprotein 1 (FMR1) gene, and causes intellectual disability in most individuals and autism or autistic behaviors in around a third of cases. Intervention options for Fragile X syndrome have historically been limited but new hope from the use of the drug as zatolmilast (BPN14770) is emerging. Various behavioral changes have been noted when using the drug under experimental conditions including those related to cognition, reading and overall daily functioning. Recruitment for a larger, phase 3 trial (longer-term, compared against a placebo) is currently underway. It is too early to say exactly how the medicine works outside of the known effects on cyclic adenosine monophosphate (cAMP), a cell messenger that regulates certain immune functions among other things. But given the drugs’ suggested usefulness in other conditions such as Alzheimer’s disease, there are likely to be multiple modes of action. The tantalizing question of whether zatolmilast and/or related medicines might be useful for some types of autism more generally remains to be investigated.
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