Autism Spectrum Disorder (ASD): Emerging Therapies

Autism Spectrum Disorder (ASD) is a developmental disability that can cause significant social, communication, and behavioral challenges. People with ASD may communicate, interact, behave, and learn in ways that are different from most other people. The learning, thinking, and problem-solving abilities of people with ASD can range from gifted to severely challenged. They might repeat certain behaviors and might not want to change in their daily activities. Many people with ASD also have different ways of learning, paying attention, or reacting to things. A diagnosis of ASD now includes several conditions that used to be diagnosed separately i.e., autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome. These conditions are now knowns as an autism spectrum disorder.

According to the U.S. Centers for Disease Control and Prevention (CDC) approximately, 1 in 68 children in the United States have been diagnosed with Autism. Autism is the third most common developmental disability. According to one of the epidemiological studies by “Action for Autism”, the prevalence rate is 1.7 million (estimated rate of 1 in 250 children). It is most frequent among the boys in comparison to the girls.

There is currently no approved drug on the market that treats the core symptoms of Autism. Hence, there are various pharmaceutical companies have the potential to transform the existing market by developing robust pioneering pipeline clinical programs to treat Autism spectrum disorder. Several companies such as Otsuka Pharmaceutical, Nobelpharma, GW Research Ltd, Hoffmann-La Roche, Allergan & Curemark are developing novel therapies.

Otsuka Pharmaceutical (Brexpiprazole)

Brexpiprazole is a molecule discovered by Otsuka and co-developed by Otsuka and Lundbeck. The efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. Brexpiprazole exhibits high affinity (subnanomolar) for these receptors as well as for noradrenaline alpha1B/2C receptors.

Brexpiprazole, is currently study under the clinical trial of Phase III. The purpose of this study is to find out about the potential benefits and safety of brexpiprazole in children and adolescent subjects, aged 5 to 17, with irritability associated with autism spectrum disorder.

GW Research Ltd (GWP42006/CBDV)

GWP42006 is the non-psychoactive cannabinoid cannabidivarin (CBDV) extracted from the cannabis plant. It has been evaluating GWP42006 in both general and syndromic pre-clinical models of ASD yielding promising signals on cognitive and social endpoints as well as repetitive behavior. These include both genetically determined abnormalities of neurobehavioral and chemically-induced models. A Phase IIa proof of concept study of a pipeline compound GWP42006 is being evaluated to treat ASD.

Hoffmann-La Roche (Balovaptan)

Balovaptan (RG7314) is a potent and specific small molecule antagonist of the V1A vasopressin receptor, which is implicated in modulating emotional processing and key social deficits exhibited in patients with Autism Spectrum Disorders. A phase III clinical trial is evaluating balovaptan for the treatment of patients with autism spectrum disorder.

Hoffmann-La Roche (RG7816)

RG7816 is a small molecule highly selective positive allosteric modulator of the GABAA α5 receptor, which is expressed in key brain regions for autism spectrum disorder.

Allergan (Cariprazine)

Cariprazine has a high affinity for Dopamine D3 receptors acting as a partial agonist at D3 receptors. Cariprazine is primarily metabolized by CYP3A4 into Desmethyl Cariprazine (DCAR) and DCAR is then further metabolized by CYP3A4 into Didesmethyl Cariprazine (DDCAR). Cariprazine, is evaluated under the clinical study of Phase-I. This study would be a multi-center, open-label, parallel-group, multiple-dose study in up to 24 male and female participants aged 5 through 17 years, inclusive, with Autism Spectrum Disorder (ASD)

Curemark (CM-AT)

CM-AT, is lead drug candidate, is designed to enhance protein digestion thereby potentially restoring the pool of essential amino acids. Essential amino acids play a critical role in the expression of several genes important to neurological function and serve as precursors to key neurotransmitters such as serotonin and dopamine.CM-AT has completed enrollment in The Blüm Study, a Phase III clinical trial for CM-AT in children aged 3-8 years old. CM-AT has received Fast Track Designation from the U.S. Food and Drug Administration (FDA). FDA has also granted Curemark a rolling review of its New Drug Application for CM-AT.

Autism Spectrum Disorder (ASD) Pipeline Landscape

Company NameProduct NameStage of DevelopmentMechanism of ActionRoute of Administration
Otsuka Pharmaceutical Brexpiprazole/OPC-34712/ LuAF41156  Phase IIIDopamine D2 Receptor Partial agonists; Serotonin 1A Receptor Partial AgonistsOral
NobelpharmaNPC-15 GranulesPhase II/III_oral
GW Research LtdGWP42006/ CBDV  Phase IICannabinoid Receptor ModulatorsOral
Hoffmann-La RocheBalovaptan/RO5285119/RO7017773Phase IIIAntagonist of the V1A Vasopressin ReceptorOral
Hoffmann-La RocheRG7816Phase I_
AllerganCariprazinePhase ICYP3A4 InhibitorOral
CuremarkCM-ATPhase IIIEnzyme ModulatorsOral

Food Allergy Awareness Week

May, 10-16 is the Food Allergy Awareness Week created by the Food Allergy Research and Education (FARE) to raise awareness regarding the different food allergies and improve public understanding of what can sometimes be a life-threatening condition.

The food allergy is an immune-mediated response to allergens in foods. When certain foods are eaten, or simply touched or inhaled, these sensitizing markers trigger the immune system into overdrive. The prevalence of food allergy is increasing worldwide. Likewise, more than 50 million Americans have an allergy of some kind. Food allergy symptoms are most common in babies and children, but they can appear at any age. It can develop an allergy to foods even eaten for years with no problems.

According to the Centers for Disease Control and Prevention (CDC), Food allergies are estimated to affect 4% – 6% of children and 4% of adults, which occurs when the immune system identifies a food or substance as a danger and triggers a protective response. This reaction may cause a wide range of symptoms, including Vomiting or stomach cramps, hives, shortness of breath, wheezing, repetitive cough, dizziness or feeling faint, weak pulse and anaphylaxis, etc. While any food can cause an adverse reaction, eight types of food account for about 90 percent of all reactions: such as eggs, milk, peanuts, fish, wheat, and soy. In addition, certain seeds including sesame and mustard seeds (the main ingredient in the condiment mustard), also are common food allergy triggers and considered a major allergen in some countries. Food allergy may also involve in affecting some other areas such as skin, the gastrointestinal tract, the cardiovascular system, and the respiratory tract.

Moreover, the food-related symptoms may occur within two hours of ingestion; often they start within minutes. In some very rare cases, the reaction may be delayed by four to six hours or even longer. The delayed reactions are most typically seen in children who develop eczema as a symptom of food allergy and in people with a rare allergy to red meat caused by the bite of a lone star tick.

Another type of delayed food allergy reaction stems from food protein-induced enterocolitis syndrome (FPIES), a severe gastrointestinal reaction that generally occurs two to six hours after consuming milk, soy, certain grains, and some other solid foods. It mostly occurs in young infants who are being exposed to these foods for the first time or who are being weaned.

Sometimes, the diagnosis of FPIES may be delayed. FPIES is a medical emergency that should be treated with IV rehydration. Allergists ask detailed questions about medical history and the symptoms for the diagnosis of food allergy. Various skin tests and/or blood tests are used for the detecting the food-specific immunoglobulin E (IgE) antibodies present in the body i.e. Skin- prick Test and Blood Test

  • Skin-Prick Tests provide results within 20 minutes. A liquid containing a tiny amount of the food allergen is placed on the skin of the arm or back and then the skin is pricked with a small, sterile probe, allowing the liquid to seep under the skin. The test, which isn’t painful but can be uncomfortable, is considered positive if a wheal develops at the site where the suspected allergen was placed. As a control, they ’ll also get a skin prick with a liquid that doesn’t contain the allergen; this should not provoke a reaction, allowing comparison between the two test sites.
  • Blood Tests which are less accurate than skin tests, measure the amount of IgE antibody to the specific food being tested. Results are typically come out in about a week and are reported in the numerical value.

The Food Allergy can be managed in the following ways:

  • To avoid consuming the food that causes problems. In addition, carefully check ingredient labels of food products.
  • Despite this, there are some other treatments to reduce minor and severe allergic reactions. e.g. For a minor allergic reaction, over-the-counter or prescribed antihistamines to reduce the symptoms. However, it can’t be used to treat severe allergic reactions.
  • For a severe allergic reaction, recommended an emergency injection of epinephrine and a trip to the emergency room. In addition, many people with allergies carry an epinephrine autoinjector (Adrenaclick, EpiPen)

During this Food Allergy Awareness Week, Whystle Launched Personalized Product Recall App to Keep Parents Informed and Families Protected. This app provides personalized safety information and up-to-the-minute recall notices, especially for up-to-date allergen recalls. Besides, every three minutes, food allergy reactions send someone to the emergency room.

Coronavirus Outbreak

Coronavirus Outbreak

Coronaviruses Description

Coronaviruses are a family of viruses that lead to respiratory illness, including the Middle East respiratory syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). It is common in many different species of animals, including camels, cattle, cats, and bats. Rarely, animal coronaviruses can infect people and then spread between people such as with MERS-CoV, SARS-CoV, and now with this new virus (named SARS-CoV-2). The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV.  All three of these viruses have their origins in bats. Similar infections are caused by human alpha and beta coronaviruses such as 229E, NL63, OC43, and HKU1.

The symptoms associated with coronavirus are the common cold, such as running nose, headache, cough, fever, and sore throat. Viruses can spread from human contact with animals. According to the World Health Organisation (WHO), scientists think MERS started in camels. Officials do not yet know what animal may have caused the current outbreak in Wuhan.

Human-to-human transmission has been confirmed for the Wuhan coronavirus, but depending on how virulent the virus is, a cough, sneeze or handshake could cause exposure. The virus can also be transmitted by touching something an infected person has touched and then touching your mouth, nose or eyes. Caregivers can sometimes be exposed by handling a patient’s waste, according to the Centers for Disease Control and Prevention (CDC). Furthermore, SARS and MERS were largely transmitted inside hospitals. Some people are also considered to be “super spreaders.”

Current Scenario

The novel coronavirus (COVID-19) was first discovered in Wuhan, China in December 2019, since then, it has affected more than 400,000 people and caused 18,440 deaths according to the World Health Organization (WHO)’s recent situation report.

The seafood market of Wuhan was identified as the suspected hub of the coronavirus outbreak by the United States Centers for Disease Control and Prevention (CDC).  Now, there have been more new cases reported from countries outside of China than from China. Two new countries/territories/areas from the Western Pacific Region and the Eastern Mediterranean Region have reported cases of COVID-19.

The mysterious novel coronavirus outbreak was identified by Chinese authorities on January 7 and since named COVID-19, is a new strain that had not been previously identified in humans. The coronavirus (COVID-19) outbreak poses a significant life-threatening and economic risk throughout the world. Over 414,179 cases have been diagnosed across 48 countries, resulting in over 18,440 reported deaths. As far as concern, due to this contagious coronavirus outbreak death has been confirmed in Hong Kong, the Philippines, Japan, France, Iran, Taiwan, South Korea, and other countries. On 31st January 2020, officially WHO has declared it a global health emergency, due to increases number of infectious cases has been confirmed in countries such as South Korea, Afghanistan, France, UAE, and many more countries.

The mortality rate is mostly within 2%~3%, well in line with the WHO official estimate. For example, MERS, SARS and the Wuhan coronavirus appear to cause more severe disease in older people Age group 60-69 years old at 3.6%, 50-59 years old at 1.4% & least 40-49 years old at 0.4%, though uncertainty remains around the latest outbreak. Of the cases of Wuhan coronavirus reported so far, none are yet confirmed to be among children.

Treatment Landscape

Several vaccines, antibiotics & anti-retroviral drugs such as FTNX-1800 (Tonix Pharmaceuticals), Leronlimab (CytoDyn), etc. are undergoing the clinical trials for coronavirus outbreak. Apart from this novel therapies, supportive therapy is also recommended including over the counter medicine for a sore throat, fever & pain reliever medications, etc. to relieve the symptoms, if happens. Additionally, drink plenty of fluids, get rest and sleep as much as possible is recommended.

Government Initiatives

The government has taken initiative to allocate the emergency funds for improving public health to curb the current global coronavirus outbreak. For instances, The Trump Administration is looking to allocate approximately $2.5 billion in emergency funds to help prepare the country should the current coronavirus crisis become a public health care threat in the U.S. Other governments and global health authorities are taking similarly aggressive steps to prepare for the virus’s continued spread. Furthermore, the UK government like Health Secretary Matt Hancock has announced that £20m in Government funding will be given to the Coalition for Epidemic Preparedness Innovations (CEPI) to advance programmes targeting the coronavirus.