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6 New Autism Medications (2015): Drugs In Clinical Trials

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that significantly affects behavior, cognitive function, and social skills.  Those with the disorder often engage in repetitive behaviors, suffer from low intelligence, and have severe difficulty verbalizing their thoughts.  In fact, a subset individuals with autism are incapable of any verbal communication and resort to gesturing (or typing) to convey their message.

Diagnoses of autism are largely subject to individual variation in that they occur across a “spectrum” of severity – meaning some autistics suffer from a greater degree of functional impairment than others.  Though some individuals with ASD are able to successfully attain an education, hold down a job, and function in society – most are unable to function independently.  As a result, they are often considered disabled and are entirely dependent upon a caretaker for survival.

While the media likes to highlight famous people with autism as being prolific writers, artists, musicians, poets, and public speakers – these celebrities typically aren’t the norm.  Most individuals diagnosed with autism have severe impairment to the extent that pharmacological interventions are required to ameliorate certain symptoms.  Though current-market medications for autism are far from perfect, pharmaceutical companies are constantly working to introduce novel, more effective options.

6 New Autism Medications (2015): Drugs in Clinical Trials

As of 2015, there are a total of 6 new medications for autism in the clinical trial pipeline.  While some of these medications hope to treat all major symptoms of autism simultaneously such as repetitive behaviors, communication deficits, and cognitive impairment – others attempt to target just one particular feature (e.g. repetitive behaviors).

  1. AT001 (Fluoxetine rapid dissolve)

  • Mechanism: SSRI
  • Company: Autism Therapeutics
  • Status: Phase III clinical trials

AT0001 is a drug under development by Autism Therapeutics, a company based in New York specifically for the treatment of “repetitive behaviors” associated with autism.  The active ingredient of AT001 is Fluoxetine, a chemical widely recognized as generic “Prozac.”  Fluoxetine functions as an SSRI, meaning it inhibits reuptake of the neurotransmitter serotonin (5-HT) – thereby increasing extracellular levels.

What’s unique about AT001 is that it incorporates a technology called “Zydis,” allowing for the Fluoxetine to be absorbed in the form of an orally disintegrating tablet (ODT).  Oral disintegration may be advantageous to swallowing a pill in that it maximizes convenience and eliminates the potential risk of choking.  Although AT001 is being tested for the treatment of repetitive behaviors associated with autism, it will likely also improve mood among those with depression.

Research from preclinical animal studies has suggested that Fluoxetine is able to reverse avoidance behaviors and ameliorate social deficits – findings which may also apply to humans with autism.  The FDA believes that this novel ODT form of Fluoxetine is promising, and thus has granted AT001 “Fast Track” designation.  Though this drug won’t bring anything new to the table in regards to pharmacological effect, and may be more costly than generic Fluoxetine, it seems as though it’s just a matter of time before it passes Phase III clinical trials and attains FDA approval.

  • Source: http://www.autismtherapeutics.com/?page_id=180
  1. CM-AT

  • Mechanism: Enzymatic modulator
  • Company: Curemark
  • Status: FDA approval (pending)

CM-AT is a drug under development by Curemark for the treatment of the core and non-core symptoms of autism spectrum disorder.  It is Curemark’s most promising pipeline drug and was considered both safe and effective in clinical trials.  Due to the preliminary safety, lack of adverse effects, and efficacy – the drug was granted “Fast Track” designation by the FDA and is currently pending FDA approval.

The drug functions primarily by targeting enzyme deficiencies among those with autism.  By correcting these enzymatic abnormalities, CM-AT is believed to increase the availability of amino acids, and thus ameliorate many core and non-core symptoms of autism including: repetitive behaviors, self-stimulation, social deficits, and hyperactivity.  The drug has also demonstrated efficacy in addressing irritability, a common non-core symptom of autism.

Though there are already multiple medications approved by the FDA for the treatment of irritability associated with autism, these medications often provoke severe side effects.  CM-AT differs from these drugs in that it isn’t associated with significant side effects and exhibits a completely different mechanism of action.  Furthermore, Curemark developers manufacture the medication with a novel lipid (oil) coating, devoid of synthetic chemicals.

CM-AT has been thoroughly tested among children (ages 3 to 8) and adolescents (ages 9 to 17) with autism.  Clinical trials revealed that the drug was both safe and effective for addressing symptoms of autism.  It is apparent that Curemark has thought outside the box with CM-AT and developed a safe, effective treatment for autism; it’s just a matter of time before this drug hits the market.

  • Source: http://curemark.com/pipeline/autism/
  1. CNDO-201 (Trichuris suis ova)

  • Mechanism: Immunomodulatory
  • Company: Coronado Biosciences
  • Status: Phase II clinical trials

Trichuris suis is considered a “whipworm” parasite that grows between 3 cm and 8 cm and lays tiny oval shaped eggs that are yellowish-brown in color.  While it may sound off-putting to consider administering porcine whipworm eggs to an individual with autism, there’s some evidence to suggest that these eggs may effectively treat symptoms.  Some experts believe that autism is caused by abnormal autoimmune responses stemming from excessively hygienic environments.

These autoimmune responses can contribute to excess inflammation and ultimately impair neurological development, possibly manifesting as autism spectrum disorders. In attempt to alter this autoimmune response, Coronado Biosciences is developing a new drug CNDO-201 which uses porcine whipworm eggs (Trichuris suis ova) as the active ingredient.  CNDO-201 is believed to act as an immunomodulatory agent, dampening heightened homeostatic immune responses.

The dampening of the autoimmune responses among those with autism is thought to decrease neuroinflammation and ultimately improve core symptoms such (e.g. repetitive behaviors) and non-core symptoms (e.g. irritability).  Currently, CNDO-201 is in Phase II clinical trials and appears to be safe (non-pathogenic) and effective.  While more research is required to verify safety and efficacy of CNDO-201 in larger populations, it may serve as a novel, futuristic treatment for autism.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23597946
  1. Memantine

  • Mechanism: NMDA receptor antagonist
  • Company: Forest Laboratories
  • Status: Phase III clinical trials

Memantine (brand name “Namenda”) is widely recognized as an FDA approved drug for the treatment of Alzheimer’s disease, but is currently in Phase III clinical investigation for the treatment of autism spectrum disorders.  Specifically, the drug is being tested for the treatment of autism (among pediatrics), pervasive developmental disorder (not otherwise specified), and asperger syndrome.  Though there are numerous theories that speculate upon the potential causes of autism, one theory is that the disorder may manifest as a result of excess glutamate – leading to excitotoxicity and neuroinflammation.

Memantine functions primarily as an NMDA receptor antagonist, thereby modulating neurotransmission of glutamate to ameliorate symptoms of autism.  In addition to its antagonism of NMDA receptors, memantine also acts as a 5-HT3 receptor and nACh receptor antagonist, as well as a D2 receptor agonist.  In other words, the drug elicits secondary effects that affect the neurotransmission of serotonin, acetylcholine, and dopamine.

Results from Phase II clinical trials suggest that memantine is likely safe and could significantly improve social responsiveness among those with autism.  Previous research among those with autism has demonstrated significant improvement in facets of behavior, language, and self-stimulation following administration of memantine as an adjunct treatment.  Preliminary evidence suggests that memantine is likely safe and well-tolerated for long-term use, but further research is warranted to elucidate its degree of efficacy among those with autism.

  • Source: http://www.neurology.org/content/82/10_Supplement/S42.009
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17690064
  1. RG7314

  • Mechanism: Vasopressin-1 receptor antagonist
  • Company: Roche Pharmaceuticals
  • Status: Phase II clinical trials

RG7314 is a drug under development by Roche Pharmaceuticals for the treatment of autism.  It functions primarily as a selective vasopression-1 receptor antagonist, meaning it selectively inhibits neurotransmission of vasopressin at the V1 receptor. Vasopressin-1 receptor antagonists are thought to alter levels of ions by modulating the flux of water via astrocyte plasma membranes.

Vasopressin receptors can be found throughout the body in the brain, smooth muscle tissues, liver, blood vessels, etc.  These receptors are known to promote vasoconstriction by increasing levels of calcium and in the brain, they may modulate blood flow to various regions. Researchers speculate that by antagonizing the vasopressin-1 receptor, RG7314 will prove most effective for treating emotional processing deficits and social impairment among those with autism.

Though it may effectively address social and emotional deficits, the specific mechanisms of action associated with vasopressin-1 receptor antagonism are unclear.  Further clinical trial research is necessary to better understand the drug’s side effects, safety, and efficacy among those with autism.  Should the drug prove safe and effective, it may be tested for the treatment of other psychiatric and/or neurological disorders besides autism.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26045648
  • Source: https://www.rush.edu/clinical-trials/rg7314-autism-treatment-study
  1. Syntocinon (Nasal Spray)

  • Mechanism: Synthetic oxytocin
  • Company: Retrophin
  • Status: Phase II clinical trials

Syntocinon is an intranasal spray developed by Retrophin that delivers a synthetic version of the hormone oxytocin to treat autism.  Preliminary research suggests that increasing the hormone oxytocin may improve social and emotional deficits associated with autism.  A study published in 2014 analyzed the therapeutic efficacy of intranasal oxytocin (Syntocinon) in 15 children diagnosed  with autism spectrum disorder.

Results indicated that the intranasal Syntocinon spray effectively reduced repetitive behaviors and anxiety, and simultaneously ameliorated social deficits.  Furthermore, this intranasal spray appeared to have lasting positive effects, persisting up to 3 months post-treatment.  It also wasn’t associated with any significant side effects or tolerability issues when administered at recommended doses.

Other studies have found Syntocinon therapeutic among adults with autism for the improvement of social cognition and quality of life.  Though further research is necessary to determine the safety and efficacy of Syntocinon among those with autism, preliminary evidence suggests that increasing oxytocin is likely to exhibit favorable therapeutic effects.

Note: It should be noted that Retrophin (the developer) is also investigating this same intranasal formulation as a new schizophrenia medication, particularly for the treatment of negative symptoms (e.g. “flat affect”).

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24508578
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23216716

Which new autism medications sound most promising? A discussion.

Of all the new autism medications in the development pipeline, the one that sounds most promising is CM-AT.  CM-AT is a novel medication developed by the company Curemark engineered to treat both the core and non-core symptoms of autism.  The drug works differently than current-market, non-targeted drugs by correcting enzymatic abnormalities to increase levels of deficient amino acids.

Unlike most other autism medications in development, CM-AT isn’t associated with significant side effects and appears safe among individuals of all ages.  To maximize tolerability, the developers (Curemark) have gone as far as to make sure the CM-AT “pills” will not contain any synthetic chemicals.  Fortunately CM-AT has finished Phase III clinical trials and has been pending FDA approval since 2013.

Assuming the clinical trials are validated and the drug meets FDA standards, it should hit the market within the next year.  Another highly promising agent to monitor is Syntocinon nasal spray under development by Retrophin.  Although it is only in Phase II clinical trials, this nasal spray appears highly effective for improving social deficits among individuals with autism.

In addition to having minimal side effects, administration of Syntocinon appears to have long-lasting therapeutic effects even following months of discontinuation.  This means that daily usage could actually have long-term benefits even after the drug is stopped.  Though Syntocinon is currently available via injection, it is being tested for autism in the format of an intranasal spray.

A highly novel, yet somewhat cringeworthy treatment for germaphobes is CNDO-201 – incorporating “Trichuris suis ova” (porcine whipworm eggs) as the active ingredient.  These eggs are derived from the parasite Trichuris suis (porcine whipworm) which doesn’t harm humans.  Upon ingestion of these eggs, the abnormally heightened autoimmune response affecting those with autism is reduced and inflammation decreases.

Another interesting drug to monitor is RG7314, which acts as a V1R (vasopressin-1 receptor) antagonist.  There aren’t many V1R antagonists on the market to treat mental illnesses and it is still relatively unclear as to how they work.  This drug is thought to primarily ameliorate social impairment associated with autism.

Lastly, the least exciting drugs in clinical trials for those with autism include Memantine and Fluoxetine ODT.  Memantine is a drug utilized primarily to treat Alzheimer’s and may address numerous symptoms among those with autism, but is a highly untargeted drug.  And while orally dissolving tablets of Fluoxetine may temporarily improve mood among those with autism, it is an untargeted and problematic long-term treatment.

Problems with current autism medications

There are numerous problems associated with currently available medications used to treat autism.  The most obvious problem is that the FDA approved interventions for autism were not specifically engineered specifically for autism and are thus untargeted.  While they may temporarily improve certain symptoms such as: brain fog, cognitive impairment, irritability, and social deficits – many drugs are problematic over a long-term.

Adverse effects: Many individuals (even children) with autism are placed on potent psychiatric drugs.  While these drugs may effectively reduce certain symptoms such as irritability, learning impairment, or social withdrawal – many carry unwanted adverse effects.  Examples of prominent adverse effects include: increased depression and suicidality, significant weight gain, dry mouth, inability to focus, etc.

Long-term effects: One fact that many professionals and pharmaceutical companies gloss over is that certain drugs are associated with debilitating long-term effects.  Even if a drug is effectively managing a symptom of autism like irritability, is ongoing treatment worth the long-term development of Type 2 diabetes? What about severe weight gain or tardive dyskinesia?

Some parents are giving antipsychotics that cause brain volume loss to their children with autism – contributing to even more functional deficits in the future.  While there are some relatively safe psychiatric drugs that can help manage autism, it is important to be aware of the more dangerous ones and utilize them only as a last resort.

Tolerance inevitability: Another problem associated with most currently available drugs to treat autism is that they’re associated with tolerance development.  While tolerance will inevitably occur with daily administration of nearly any substance, it is something that needs to be understood.  Many people are confused when drugs like antidepressants stop working and they fail to realize that an individual’s neurophysiology has become tolerant to the drug’s effect.

This tolerance may not be problematic initially if the individual was taking the minimal effective dose and only requires a small increase in dosage for continued drug efficacy.  However, it often becomes a problem over time when the dosage reaches higher levels – inevitably causing more severe, debilitating side effects; the greater the dose – the greater the biological toll.

Untargeted: Autism as a disorder is poorly understood, and most approved drugs for the treatment of symptoms are nothing more than a hodge-podge of “off-label” options that have been recommended by professionals.  Few of these drugs have gone through rigorous testing in samples of those diagnosed with autism.  Although these drugs are the best available options to treat certain symptoms, they fail to address the root of the condition.

Withdrawal symptoms: A bulk of agents used to treat autism are associated with horrendous discontinuation effects.  Often these effects linger for weeks, months, or sometimes longer – making it difficult to distinguish the withdrawal from the original illness.  This further complicates psychiatric treatment due to the fact that psychiatrists often fail to consider post-acute discontinuation effects.

A drug taken for an extended period of time often causes a chemical imbalance that takes much longer than a few days (or week) before an individual’s neurotransmission reverts back to a homeostatic baseline.  Even more difficult is the fact that upon discontinuation of a psychiatric drug, an individual with autism may be unable to properly express their inner experience to others.  Outsiders may perceive that the autism has merely worsened rather than considered that the individual is undergoing withdrawal from a medication.

Ways to improve autism medications for the future

There are several ways in which pharmaceutical companies could improve upon existing autism medications in the future.  As our understanding of the entire “spectrum” is enhanced with ongoing neuroscientific research, the neurophysiological and genetic origins will be pinpointed.  When better theories regarding the causes of autism emerge, pharmaceutical drugs should be engineered with the intent of targeting those specific causes – rather than merely patching symptoms.

  • Targeted effects: New drugs should aim to target the specific neurophysiological and/or genetic underpinnings of autism. Upon designing new drugs, pharmaceuticals should consider whether they are effectively treating the core symptoms of autism or acting as a patch to cover up one specific symptom (e.g. irritability).  While a “good patch” is better than no patch at all, developing one drug that ameliorates all core symptoms would provide more substantial benefit.
  • Drug delivery: Pharmaceutical companies should be considering all potential options for drug delivery. Testing new delivery strategies such as a long-acting intramuscular injection, intranasal sprays, orally dissolving tablets, sublingual films, etc. – may be beneficial.  Certain strategies may improve patient-compliance and minimize likelihood of side effects compared to a standard “pill.”
  • Lingering benefit: Rather than design a drug with horrific withdrawal symptoms, companies may want to consider designing agents that have lingering therapeutic effects. In other words, drugs should be designed to treat symptoms while they are taken, but the beneficial effects should linger upon cessation of treatment.  While it would be challenging to design such an agent, it is theoretically plausible if considering that hallucinogens like psilocybin often exhibit lingering benefits.  It also may be possible someday to take a psychiatric drug like a person would take an antibiotic when sick; administer it for a few weeks and get a permanent beneficial effect.
  • Safety: Pharmaceutical companies should aim to create safer drugs in regards to potential for adverse effects and even general side effects. New agents should have minimal adverse effects and reduced likelihood of tolerance and/or withdrawal symptoms.  Furthermore, efforts should be made to decrease contraindications with other medications.

Which new autism medications are you most excited about?

Although we are a long ways away from “curing” autism, there are many promising, novel treatments in the pipeline.  These drugs have potential to improve cognitive and social functionality among those with severe forms of the disorder.  Furthermore, they have significant potential to improve the quality of life for those suffering severely as a result of their condition.

While some high-functioning individuals with autism believe that the disorder should not be “cured” or treated to preserve neurodiversity, others with more severe forms would be thankful for a new treatment that could ameliorate debilitating symptoms.  If you or someone you know has autism, which medication in development do you believe has the most promise?  Feel free to share your thoughts in the comments section below.

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