A clinical research site in Warwick is testing a drug that may be the first pharmaceutical treatment for autism beyond intense antipsychotics. 

The trial is currently taking place at Omega Medical Research on Bald Hill Road near Warwick Mall, one of over 30 sites across the U.S. participating in a study run by Curemark.

A biopharmaceutical company based in Rye, New York, Curemark focuses on neurological developmental disorders, such as Parkinson’s disease and schizophrenia, in addition to autism. In this trial, they are testing the proposition that an enzyme deficiency in autistic children is, through a biological chain of events, generating the behavioral symptoms that form part of the autism spectrum disorder. 

In the 1990s, founder of Curemark Dr. Joan Fallon noticed that a majority of autistic children in her clinical practice were missing the enzyme chymotrypsin, which allows the body to process certain proteins. This was before Curemark existed, and so Fallon assembled various over-the-counter medications to treat the enzyme deficiency in her patients. Soon, these patients began manifesting behavioral shifts. 

Years later, Curemark has developed a pancreatic enzyme to replicate this treatment. Called CM-AT, the drug is a tan, granular powder, pharmaceutical-quality and highly refined, that is sprinkled on the child’s food several times a day by a caregiver. 

When this enzyme is deficient in the body and unable to process protein in certain ways, the pool of amino acids in the body becomes deficient as well. Amino acids have effects on the body far beyond the digestive system, they impact the ability of certain genes to express themselves, genes that help neurotransmitters in the brain to fire correctly. This means that the enzyme deficiency may lead to neurotransmitter issues, which may cause certain effects to central nervous system behaviors. Replacing the missing enzyme restores the ability of the body to digest all proteins, the genes to signal the way they’re supposed to, and the neurotransmitters to work.

Promising drug

Certain behaviors cannot be tied, at this time, to specific amino acids. Despite this lack of specifics, though, the trial is well on its way and has even been fast-tracked by the FDA. Dr. Matthew Heil, chief scientific officer at Curemark, points out that “you don’t have to know how something works to get it approved” by the FDA. Antidepressants, for example, do more than simply restoring serotonin levels, but their efficacy in combating depression has not yet been fully explained by science. Fast-tracking is usually afforded to “a drug that is promising for an urgent, unmet medical need,” says Heil, who manufactures the drugs for Curemark’s trials and examines the data that Curemark receives from its clinical sites; the agency commits to a six-month review time and accepts pieces of the study as they are completed rather than requiring that the whole project be submitted at once. This trial may have been particularly attractive because, at the moment, “there is no drug treatment for autism” beyond two antipsychotic drugs with powerful side effects. Existing autism treatments, like applied behavioral analysis (ABA), aim for behavioral modification through reinforcement. 

Heil emphasizes that Curemark’s roots are in clinical modifications, not theoretical investigations – taking action based on observations, rather than accumulated scientific data. Adding this enzyme to autistic children’s diets seems to have an effect, but the scientific minutiae behind those effects are still hazy. This may not bother the parents of children with autism, many of whom are likely to have attempted multiple dietary interventions such as removing gluten and dairy from their diets or amping up their consumption of probiotics. Autistic children often have eating difficulties that include extreme selectivity, gastrointestinal pain, and constipation.

“Children with this enzyme deficiency,” Heil says, are likely experiencing incomplete digestion leading to inflammation of the gut – this may lead them to self-select a restricted diet.

 CM-AT has therefore been designed to be imperceptible to the child, both tasteless and odorless. It has also been designed to be harmless: enzymes can have wide-ranging effects once they’re out of the stomach, and “will digest your food and your skin just as happily,” Heil points out. “An enzyme burn can be quite nasty.” He explains that the CM-AT particles are coated in a lipid so that they won’t activate until they reach the first part of the small intestine, where digestion occurs and amino acids are absorbed. This means it also won’t activate on the caregiver’s hands as he or she opens the package containing the powder.

One thing that is physiologically wrong

Of the enzyme deficiency, Heil says, “I don’t know if this is the only thing that is going on in these autistic children” but “it’s one thing that is physiologically wrong” – a thing that could be combining with other physiological aspects of the child to produce “the symptom behaviors.” Autism spectrum disorder itself is characterized, in the Diagnostic and Statistical Manual, as a broad group of behaviors from which autism is diagnosed. The symptoms include irritability; temper tantrums; frustration in reaction to sensory input such as sounds, interactions, colors, and light; hyperactivity; profound speech disability (inability to speak, or ability only to echo what is said to them); and difficulty interacting with others. Currently, one in 68 children are diagnosed with autism. 

Given the fact that protein in the gut may be affecting communication in the brain, could dietary modifications change behaviors as well? Absolutely not, says Heil. “The deficiency in the enzyme that these children manifest can’t be induced.” Even depriving yourself of all protein wouldn’t reduce your enzyme levels so drastically. 

Children from 3 to 8 years old are included in the study, and are compensated for their participation. After a 14-week study in which some participants are given placebos (and neither the participants nor the clinicians know what anyone is getting), a 72-week open-label study follows in which all participants receive the enzyme. Regular stool samples indicate to clinicians whether the pools of amino acids in patients are regenerating.

 Children without the enzyme deficiency are also included in Curemark’s clinical trial, per the FDA’s request. The precise cutoff point between deficient and appropriate amounts of the enzyme is somewhat random; testing children with varying levels of the enzyme will therefore help the researchers determine if supplying the enzyme can help those who don’t have the deficiency, or whose enzyme levels are borderline acceptable. This information will determine the precise instructions given to those who may eventually be prescribed the drug, and whether insurance companies will or will not reimburse those who buy it.

 So far, the treatment seems to affect children with autism of varying severities, and of different ages.  Older children have been included in the open-label trials around the country, and the effect of the enzyme has been shown to persist in them, and to deepen over time. In fact, the drug seems to have more and more effects the longer that the child takes it. “Based on that experience,” Heil says, “I would expect that the drug will continue to be efficacious throughout life.” That enzyme deficiency can never be fixed, so if and when the drug is prescribed, those taking it will have to do so for the rest of their lives.

At the moment, CM-AT seems to be a hit: 95 percent of children who have gone through the first, 14-week trial choose to continue to the 72-week open-label trial, even those who received the placebo in the first trial. Part of the reason for the open-label trial is to give those parents who have received the placebo a chance to receive the real thing.

 There’s a long way to go, though, before science sheds a light on why autism occurs and what causes its trademark behavioral manifestations. The current lack of data in the field seems to have led to intense conflict over its causes and whether rates of incidence or detection have risen. A scientist affiliated with Brown University who studies early signs of autism, as well as a teacher who works with autistic students, chose not to comment for this story. There may be controversy among those who work on autism-related issues around pharmacological interventions with this population, connected to conflicts between the medical model of disability, which posits disability as a problem to be fixed, and the social model of disability, which advocates for changing environments to fit the needs of those with disabilities. While the medical model might suggest behavioral modifications designed to help the child’s behaviors match those of the non-autistic population, the social model might propose changes to lights, sounds, and smells in a classroom to help a child with heightened sensitivity.

Despite the clouded nature of information on autism, however, Heil seems certain that Curemark has seized on a verifiable piece of it. “As we learn more about it,” Heil says, autism “may have big subgroups, ways that children get to that endpoint of behaviors.” The enzyme deficiency, in more than 60 percent of autistic children, is not “the main cause or the only cause” of autism, Heil says. But, he believes, it’s “a major contributing factor.”