Autism, Alzheimer, multiple sclerosis, schizophrenia, Parkinson, cerebral palsy, epilepsy, dyslexia, and stuttering, are they a preventable single disease?

In 2022, the US spent $13,493 per person on healthcare. This is double

the average costs compared to other developed countries and represents

$4.5 trillion in total US healthcare spending. Of this amount, it is estimated

that more than one third ($1.6 trillion) is spent on treatments for the listed

diseases.

ABSTRACT

Autism, Alzheimer, multiple sclerosis, schizophrenia, Parkinson, cerebral

palsy, epilepsy, dyslexia, and stuttering are, for purposes of this article, a

single disease of the brain and central nervous system. This single disease

is thought to have a single cause, the toxins of the bacterium Clostridium

perfringens, a common human gut inhabitant. The most damaging toxin is

the epsilon toxin, which forms pores in the blood brain barrier. This increased

permeability allows other toxins (alpha, beta and enterotoxin) to pass through

this barrier and cause damage to the brain and central nervous system.

Knowledge of these toxins can be used to create a vaccine from inactivated

toxins, called toxoids. A toxoid-based vaccine that prevents this disease will

reduce suffering and save more than $1 trillion in annual US healthcare costs.

INTRODUCTION

It is generally accepted that the cause of the diseases named in the title are

‘unknown’ and treatments involve suppression of symptoms. The goal of this

article is to propose a vaccine for prevention of these ‘diseases’, through

an attack the cause approach. With autism spectrum disorder (ASD), a Web

of Science search for the phrase “early birth ASD” results in approximately

2,000 papers, which suggest that either preterm births (before 37 weeks)

or underweight births (less than 5 pounds, 8 ounces) are a cause of autism,

when they are likely symptoms. It is proposed here that the nine diseases

are caused by a combination of toxins from Clostridium perfringens (C.

perfringens), with the epsilon toxin creating the conditions through which

all the toxins can cause brain and central nervous system (CNS) damage. If

these toxins are responsible for all the diseases listed, then prevention per a

single vaccine is logical. A toxoid-based vaccine is the ideal candidate and

would optimally be delivered prenatally to expecting mothers, and postnatally

through inoculations with boosters.

This article proposes that the symptoms of the disease are a result of C.

perfringens toxins affecting the developing fetus by traveling from an infected

mother via the umbilical cord, causing damage to the fetus resulting in either

miscarriage, preterm birth and/or low birth weight depending on the amount

of toxin exposure and stage of fetal development. A large amount of toxin

reaching the fetus may result in miscarriage, while lesser amounts could

result in preterm birth, autism and cerebral palsy. The incidence of cerebral

palsy is 2 in 1,000 full-term births but increases to 112 in 1,000 preterm [2].

If C. perfringens toxins are responsible, the development of a toxoid-based

vaccine would be modeled after a vaccine developed almost a century

ago for another member of the same bacterial genus, Clostridium tetani (C.

tetani): the causal agent of tetanus. A toxoid-based vaccine against C. tetani

toxins is currently used in the vaccine against diphtheria, whooping cough

(pertussis) and tetanus (DPT). The DPT vaccine is one of the oldest and most

widespread used vaccines in worldwide use and has had an excellent safety

record during that timeframe. The World Health Organization (WHO) suggests

that neonatal tetanus can be prevented by immunizing women of reproductive

age either prior to pregnancy or during pregnancy with few safety issues.

Similar arguments can be made for the same vaccine per involvement of C.

perfringens toxins in the other neurological diseases listed.

THE DISEASES

Approximately 90 million people in the US are afflicted by the nine diseases

listed in the title. The diseases are each briefly described, along with the

commonalities between the diseases, in terms of cause and preventative

approach.

Multiple sclerosis (MS) is a chronic, progressive neurodegenerative

disease with a complex pathophysiological background [3]. While the cause

of MS is usually stated as unknown, it is thought that something triggers

the immune system to attack the CNS, which makes MS an autoimmune

disease. The resulting damage to myelin, the protective layer insulating wirelike

nerve fibers, disrupts signals to and from the brain. This interruption of

communication signals causes unpredictable symptoms such as numbness,

tingling, mood changes, memory problems, pain, fatigue, blindness and/or paralysis. Everyone’s experience with MS is different and these losses may be

temporary or long lasting [4]. The prevalence of MS in 1976 was 6 people per

10,000. This number more than doubled to 15 per 10,000 in the period from

2008 to 2012, with a female to male ratio of 3:1 [5].

Autism, according to most literature, is a developmental disability of the brain

that can begin to manifest itself before the age of three years and can last

throughout a person’s life although some symptoms may improve over time

with some people who have been diagnosed with Autism can live productive

lives. However, many of those diagnosed need specialized care that can

require vast resources of time and money. Researchers believe there could

be multiple causes of autism, including genetics and environmental factors.

Even though risk factors have been identified, current treatments focus on

symptoms. It is proposed here that autism involves brain damage that is

caused by C. perfringens toxins. The epsilon toxin is most likely involved in

periodically increasing the permeability of the BBB, which has the primary

prevention task of barring foreign compound entry into the brain. Alpha, beta

and enterotoxin are also likely to participate in entry and damage of the brain

and CNS.

Schizophrenia is a brain characterized by delusions, hallucinations,

trouble with speaking and thinking that affects about one percent of the US

population. The cause is currently unknown. There is no known cure, and

research is aimed at treating the symptoms. This disease afflicts young men

and women equally although its onset is earlier in men, typically in late teens

to early twenties, while in women it occurs in the late twenties to early thirties.

Schizophrenia afflicted people usually die young, often due to comorbidity

with heart disease and diabetes [6]. More than 50% of mass shooters have

been earlier diagnosed with schizophrenia. Of the others, more than half

have been diagnosed with ‘mania’ or similar mental disorders. As victims of

schizophrenia, they likely have been rejected for friendships and/or teased

for being ‘strange’ by other children or coworkers. This rejection and criticism

may lead to efforts to get retribution and revenge, resulting in mass shootings.

The revenge and retribution seem like ‘confabulation’ in some older males

with Alzheimer.

Alzheimer is a chronic brain disease that is characterized by progressive

memory loss while being the most common cause of dementia [7]. Typically,

Alzheimer manifests in people aged 65 and older, however early-onset is

possible. As with the other diseases listed, the cause is currently unknown

while various researchers believe there could be multiple causes. There

is evidence showing that a dysfunctional BBB is involved with Alzheimer

cognitive decline [7]. In early stages symptoms can include agitation, anxiety,

mood swings as well as a decrease in mental abilities [8]. As this disease

progresses, so do the symptoms. It is possible in later stages that the patient

can experience delusions, hallucinations and ultimately a vegetative state

of minimal activity [7]. In a minority of cases of confabulation in Alzheimer,

the victim will believe, most or all evidence to the contrary, that everything

the confabulator does is perfect and anyone not in agreement is the enemy

and must be met with retribution and revenge. It is thus possible that young

schizophrenic males and older Alzheimer confabulators may be a continuum

of a single disease that may encompass violent revolutionaries of small

countries to the confabulation-driven would-be emperor or president of a

larger country. There is a 2023 FDA-approved treatment known as Leqembi

that helps remove the amyloid plaque that appears in the brain. This

treatment assumes that amyloid plaque is causally related to Alzheimer and

not just a symptom of the disease.

Parkinson is a chronic progressive degenerative disorder of the CNS that

affects both the motor system and mental systems. Early symptoms are

tremors, rigidity, slowness of movement and difficulty walking. As the disease

progresses, cognitive symptoms become more common. Problems may also

arise with behavior, sleep, and sensory systems, while dementia is common in

advanced stages [9]. While diagnosis of Parkinson is usually based on motor

related symptoms, there is evidence of increased permeability of the BBB

using cerebrospinal fluid analysis and positron emitting tomography imaging

[10]. Parkinson typically occurs in people over the age of 60, of whom, about

one percent are affected. The average post-diagnosis life expectancy is 7

to 15 years. No cure for Parkinson is known, and treatment aims to mitigate

symptoms [11].

Cerebral palsy is a group of non-progressive movement disorders that

appear in early childhood. Signs and symptoms vary among people and over

time but include tremors, poor coordination, stiff and/or weak muscles [12].

There may be problems with sensation, vision, hearing, and speech. Often,

babies with Cerebral palsy do not roll over, sit, crawl or walk as early as other

children. Other symptoms include seizures and problems with thinking or

reasoning. While symptoms may get more noticeable over the first years of

life, underlying problems do not worsen over time. Cerebral palsy is caused

by abnormal development or damage to the parts of the brain that control

movement, balance, and posture [12]. Most often, the problems occur during

pregnancy but may occur during childbirth or shortly afterwards. Often, the

cause is stated as unknown.

Epilepsy is a group of non-communicable neurological disorders

characterized by recurrent epileptic seizures [13]. An epileptic seizure is the

clinical manifestation of an abnormal, excessive, and synchronized electrical

discharge in the brain cells called neurons. Epileptic seizures can vary from

brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain [13]. In epilepsy, seizures tend

to recur and may have no detectable underlying cause. People with epilepsy

experience varying degrees of social stigma due to the alarming nature of

their symptoms.]As of 2021, there were 3.4 million people (approximately 1%

of the population) with epilepsy in the US. It is known that BBB dysfunction is

critical in epilepsy [14].

Dyslexia is the most common neurobehavioral disorder in children and young

adults, affecting 20% of the population [15]. More than 66 million people

suffer from dyslexia, the symptoms of which are difficulty in reading writing

and math but also may include difficulty with movement and understanding

the concept of time. While some of the symptoms can be improved by

specialized instruction, probably a better way of handling the problem is to

attack the cause of this mental health problem. Dyslexia represents 80% of all

learning disabilities [16].

Stuttering is a speech pattern involving involuntary disruptions, or

“disfluencies”, in the forward flow of speech. Stuttering usually begins in

childhood before the age of five and is not progressive. It is estimated that

about 1% of the US population stutters, though about 5% of children go

through a period of stuttering. In children the ratio is 2:1 male to female while

in adulthood it is 4:1 male to female [17].

CLOSTRIDIUM BACTERIA NEUROTOXINS

The proposed cause for nine diseases in this article is the toxins produced

by Clostridium perfringens. Clostridia species are anaerobic, rod-shaped

spore-forming bacteria that make the most potent bacterial toxins known.

For example, some of the toxins that Clostridium botulinum (C. botulinum), C.

tetani and C. perfringens produce are considered potential biological warfare

agents.

C. botulinum toxin is the most potent bacterial toxin, and botulism can

cause lethal lung and heart muscle paralysis. Although it can be found in

contaminated canned food, Botulism is a rare disease, and the bacterium

is not part of the typical human gut microbiota. Despite its toxicity, a greatly

diluted botulinum toxin is FDA-cleared to reduce wrinkles in aging skin

(Botox ®).

C. tetani toxin is second most potent bacterial toxin, and tetanus can cause

lethal muscle seizure in the jaw and neck. The bacterium is common in the

environment and readily infects unvaccinated people via open wounds. A

toxoid-based vaccine created almost a century ago has greatly reduced

worldwide infections. Adoption of the vaccine in the US then and later by

the World Health Organization (WHO) has proved highly successful against

tetanus [18].

C. perfringens epsilon toxin is the third most potent bacterial toxin [19].

This species is ubiquitous in water and soil and colonizes both the human

and animal gut. C. perfringens is a major cause of food poisoning from

undercooked beef and poultry and spores can survive normal cooking

temperatures [20]. As C. perfringens is one of the most rapidly duplicating

species with a doubling time under ten minutes, even a small number of

cells can dramatically increase in number per favorable conditions. During

favorable growth, toxin production is increased, with rapidly declining

toxin production when less favorable conditions return. Favorable growth

conditions can occur per several common occurrences (1) oral antibiotics can

kill many beneficial gut bacteria and dormant spores switch to an active rapid

growth phase, (2) high fructose corn syrup (HFCS) presence in the human

diet enhances growth. Although HFCS is banned or partially banned in some

countries, its use in the US is still common. Of note, the fructose in HFCS is a

key component of semi-selective growth media for isolation of clostridia.

C. perfringens produces twenty toxins, with the most significant toxin being

the epsilon toxin, a pore-former that can increase the permeability of the

blood brain barrier (BBB). Other toxins of human concern are the alpha toxin

which causes food poisoning but can also break down phosphatidylcholine

and sphingomyelin in cell membranes, which are associated with MS. The

pores formed by the epsilon toxin also allow the beta and enterotoxin to pass

into the brain and damage neuronal cells [20].

In cattle, epsilon toxin is known to cause the lethal disease enterotoxemia.

Of human significance, this pore-forming toxin is thought to initially enter

the circulatory system through the gut epithelial lining and then ultimately

breaches the BBB potentially causing the neurodegenerative diseases

listed. Epsilon toxin causes permeability in the BBB by binding to the myelin

and lymphocyte protein receptor forming a pore which compromises the

selectivity of the BBB allowing for epsilon toxin to enter the brain [21]. Proper

brain function and health require an intact BBB, otherwise blood borne toxins

can enter the brain. There is evidence showing that MS could be caused

by epsilon toxin. The first suggestion of an association between exposure

to epsilon toxin and the development of MS was made by Murrell et al in

a 1986 paper [22]. Out of a group of 8 researchers working on swayback

disease in lambs, 5 of them subsequently developed MS. Since lambs are

colonized by C. perfringens which produces epsilon toxin, it was suggested

that these researchers were exposed to the toxin. According to Dean et al, the

probability of this happening by another mechanism is about one in a billion.

Furthermore, according to Yinhua Ma et al, the gut microbiota of MS patients

was more likely to harbor a greater abundance of epsilon toxin-producing C.

perfringens strains than healthy controls and isolates from these patients with

MS produced functional epsilon toxin [22]. VACCINES

A toxoid vaccine is proposed against C. perfringens alpha, beta, enterotoxin

and epsilon toxins, for prevention of the nine diseases in the title, as well

as prevention of food poisoning. A precedent for a toxoid vaccine is the

original tetanus toxoid vaccine (from C. tetani), first licensed in 1937. The

diphtheria vaccine (Corynebacteria diphtheriae) which was created in 1923,

and subsequently recommended by WHO, caused a 90% global decrease

in diphtheria by the year 2000. Few negative side effects have been reported

and it is accepted as safe for pregnant women. It is recommended that

pregnant women be vaccinated to prevent maternal and neonatal tetanus.

The pertussis toxin (Bordetella pertussis), the cause of whooping cough,

is another toxin capable of penetrating the BBB and can cause severe

neurological complications. The original vaccine for pertussis was licensed in

1914. Currently one of WHO’s most widely used vaccines is the combination

vaccine against diphtheria, whooping cough (pertussis) and tetanus (DTP),

which is one of the oldest vaccines approved for human use [24]. The

currently licensed version of this vaccine has been studied to show long-term

safety and efficacy [25]. The combination vaccine for DPT has been used for

almost a century, and WHO recommended that the DPT vaccine be used in all

countries due to its efficacy [18]. The DPT immunization schedule are doses

at ages two, four, and six months followed by a dose at eighteen months and

another vaccination at six years of age.

By extension it seems logical that a vaccine against diseases caused by

C. perfringens toxins would be effective, as there are currently no human

vaccines against the C. perfringens epsilon toxin [26]. Given that the vaccine

would also include the alpha, beta and enterotoxin would give additional

neuroprotective benefits and prevent food poisoning by the same bacterium.

C. perfringens toxoid vaccines do however currently exist for use in cattle and

other livestock. Just as the DPT vaccine is highly effective against their target

diseases and are proven per almost a century of world-wide use, the vaccine

proposed here will hopefully be similarly effective and safe for use. The safety

of the tetanus vaccine is significant as C. tetani and C. perfringens are closely

related pathogens, both producing toxins that target the BBB.

CONCLUSION

With billion-to-one odds for the cause of MS being the toxins of C.

perfringens [22], a toxoid-based vaccine should have a profound impact on

MS. Assuming the other diseases (in the title) are linked to the same bacterial

toxins, a single vaccine could prove to be a significant new approach for the

population that is either directly or indirectly impacted by these nine diseases.

The toxoid-based DPT vaccine, with its long-term efficacy and safety record,

serves as a model for disease prevention from toxin-producing bacteria. If

the proposed vaccine leads to the prevention of all nine ‘diseases’, an annual

savings of greater than $1 trillion is feasible. Additional ‘beneficial side effects’

would include an instant reduction in a leading cause of food poisoning.

A successful example of attacking the cause is the case of Australian

Professors Barry Marshall and Robin Warren, whereby the true cause of

gastritis and peptic ulcer disease was elucidated. Their discovery of the

bacterium Helicobacter pylori as the true causal agent of most Peptic ulcer

disease, as opposed to stress or environmental factors.

WHO WOULD BE OPPOSED TO THIS APPROACH?

• Big Pharma, whose drugs cause damaging side effects.

• Internal NIH Researchers, rewarded by journal article numbers.

• NIH-funded University Faculty, who submit millions of articles.

• Scientific journals, that need those articles to stay in business.

• Centers for Disease Control & Prevention, who also write journal articles.

References

[1] Sources of estimates: National non-profit organizations, NIH National Institute of

Mental Health, NIH National Institute on Aging, CDC MMWR

[2] https://doi.org/10.1177/08830738211059686

[3] https://doi.org/10.3390/cells12131760

[4] https://www.nationalmssociety.org/understanding-ms/what-is-ms

[5] https://www.neurology.org/doi/10.1212/WNL.0000000000007035

[6] https://www.psychiatry.org/patients-families/schizophrenia/what-is-schizophrenia

[7] https://doi.org/10.1016/j.pharmthera.2022.108119

[8] https://doi.org/10.3233/JAD-180688

[9] https://www.ninds.nih.gov/health-information/disorders/parkinsons-disease

[10] https://doi.org/10.1038/jcbfm.2015.32

[11] https://doi.org/10.1016/S0140-6736(14)61393-3

[12] https://www.ninds.nih.gov/health-information/disorders/cerebral-palsy

[13] https://www.who.int/en/news-room/fact-sheets/detail/epilepsy

[14] https://doi.org/10.1111/bpa.13147

[15] https://doi.org/10.1007/s40817-020-00094-3

[16] http://dx.doi.org/10.1016/j.jpeds.2015.07.045

[17] https://westutter.org/facts-about-stuttering/

[18] https://doi.org/10.1016/j.vaccine.2017.02.034

[19] https://doi.org/10.1016/j.anaerobe.2014.08.016

[20] https://www.ncbi.nlm.nih.gov/books/NBK559049/

[21] https://doi.org/10.1371/journal.ppat.1008014

[22] https://doi.org/10.1177/13524585231186899

[23] https://doi.org/10.2217/fmb-2021-0167

[24] https://doi.org/10.1542/peds.2017-4171

[25] https://doi.org/10.1016/j.vaccine.2009.07.047