Over 1.1% of the world’s
population is diagnosed with schizophrenia. It is estimated
that the United States alone has approximately 3 million cases
of schizophrenic people.In the
past, extensive research was conducted, but scientists still
have little knowledge about the disease and what causes it.
Currently, drugs are effective at treating hallucinations and
paranoia, symptoms common in schizophrenia, but researchers
still have not identified a treatment for cognitive problems
and social difficulties caused by the disease.
An average person has a
1 in 100 chance to develop schizophrenia. While the exact
cause of the disease is still unknown, research suggests there
are various factors that may contribute to developing the
illness. Genetics, brain development, and neurotransmitters
may play a role.A single genetic
mutation known as 22q11 can increase the chance of
schizophrenia by a ratio of 1 to 4.
Another increase in risk
for developing the disease may result from a large number of
smaller mutations.Changes in the
brain’s structure also occur in some people with the disease,
which suggests the disease may be a disorder of the brain.
Studies demonstrate that unbalanced amounts of
neurotransmitters, dopamine, and serotonin may lead to
conditions associated with schizophrenia.
Innovative research and
development efforts pertaining to schizophrenia are now
eligible for R&D tax credits.
The Research & Development Tax
Credit
Enacted in 1981, the federal Research and Development
(R&D) Tax Credit allows a credit of upto
13% of eligible spending for new and improved products and
processes. Qualified research must meet the following four
criteria:
New or improved products,
processes, or software
Technological in nature
Elimination
of Uncertainty
Process of Experimentation
Eligible costs
include employee wages, cost of supplies, cost of testing,
contract research expenses, and costs associated with
developing a patent. On December
18, 2015, President Obama signed the bill making the R&D
Tax Credit permanent. Beginning in 2016, the R&D credit
can be used to offset Alternative Minimum tax and startup
businesses can utilize the credit against payroll taxes.
Symptoms of the Disease
Although schizophrenia symptoms vary per individual, they all
negatively impact a person’s ability to function normally.
Major symptoms comprise of delusions, hallucinations, abnormal
motor behavior, poor memory, and disorganized thinking.
Certain behavioral
symptoms include a lack of emotion, not making eye contact,
lack of motivation, depression, social withdrawal, and a
decrease in being able to express emotions. Living with
schizophrenia puts a strain on an individual’s everyday
activities, which is why researchers are determined to
discover more about the disease and find a cure.
Researching Schizophrenia
Stem Cell Research
The New York Stem Cell
Foundation (NYSCF) and the Stanley Center at the Broad
Institute of MIT and Harvard work together in stem cell
research to uncover more information about schizophrenia.
NYSCF engineered stem cell lines from skin samples of
patients, whose information was supplied by the Stanley
Center. These skin samples are developed into induced
pluripotent stem (iPS) cell lines.
An innovative robotic
machine, The NYSCF Global Stem Cell Array, was utilized to
produce multiple amounts of stem cell lines. Once the iPS
cells grew, they were transformed into adult brain cell models
affected by schizophrenia. iPS cells are ideal for research
purposes because they offer endless supplies of diverse cells.
Stem cell studies allow scientists to broaden their span of
research to explore the unknown of any disease.By analyzing stem cells, researchers get an in-depth
view into how schizophrenia actually impacts our cellular
composition.
Mouse Model Developments
A mouse is 99% similar
to a human, which makes it a preferred model for genetic
testing in lab research and experimentation.In 2007, researchers from Johns Hopkins University
developed the first mouse model intended for schizophrenia
research. The engineered mouse was designed to model
anatomical and behavioral effects of the disease. The mice
models had a shortened form of DISC1 protein, which disrupted
their usual functions. Observations were made about the mice
pursuing their daily activities.
It was found that the
mice experienced similar behavior to patients with
schizophrenia. They exhibited difficulty finding hidden food,
were restless when put in an open field, and were not capable
of swimming as long as normal mice.Thus,
mice models play a significant role in lab research because
they help scientists investigate unknown facts about diseases
without experimenting on humans.
The National Institute
of Health also contributed in funding the Brain Research
through Advancing Innovative Neurotechnologies (BRAIN)
initiative program. In this program, researchers studied how
the brain functions.The premise
of this program is to develop new tools that can assist in
treating brain disorders and diseases.
Designer Receptors
Exclusively Activated by Designer Drugs (DREADD) 2.0 is a tool
created to control neurons. The tool affects a synthetic brain
chemical messenger system that connects with the body’s
natural systems. Researchers developed mice models with
designer receptors that attach to synthetic proteins located
on neurons.A designer drug binds
to its receptor and can either block or set off neuron
activity depending on how researchers program the components.
DREADD 2.0 affects the designer receptors and drugs, which
permits researchers to control mice models’ brain circuits and
any associated behaviors.
Drugs in Development for
Schizophrenia
ITI-007
Intra-Cellular Therapies
is a biopharmaceutical company whose focus is to develop drugs
for the treatment of diseases in the Central Nervous System
(CNS). While developing drugs, Intra-Cellular Therapies
utilize a state-of-the-art platform, CNS Profile, to select
compounds with the highest potential to treat disease. This
company is currently testing a pill that focuses on working
directly inside neurons instead of outside them.
Intra-Cellular Therapies
have been experimenting with a schizophrenia drug known as
ITI-007. ITI-007 is an oral drug that impacts the dopamine
receptor modulation in order to reduce symptoms associated
with the disease. Presently, the drug passed the first of two
Phase III trials. During the Phase II trial, the 60 mg dosage
reached all the primary and secondary goals, but the 40 mg
dosage wasn’t as successful. The 60 mg drug improved user
scores on the Positive and Negative Syndrome Scale (PANSS) and
the Clinical Global Impression Scale for Severity of Illness.
So far, it is proven through trial results that the drug has
positive effects on patients. Regardless, ITI-007 must go
through the second Phase III trial and pass FDA standards.
Encenicline
Forum Pharmaceuticals is
a biopharmaceutical company in the process of creating a drug
called Encenicline, which serves as a treatment for cognitive
impairment. Encenicline is an oral medicine that is an agonist
of the alpha 7 receptor. Encenicline targets the alpha 7
receptor to increase its response to acetylcholine, which is
believed to improve sensory gating, attention, and cognition.
Phase II results were
recently released to the public, which demonstrate positive
outcomes. The study examined the safety and effectiveness of
the medicine when people took two doses. These doses helped
patients with cognitive impairment in completing normal
day-to-day actions. The end results helped the company plan
trial designs and distribution of dosage amounts during the
next Phase III trials.
The FDA has given Forum
Pharmaceuticals access to the Fast Track Program. This program
quickens the process of developing and reviewing drug
candidates with the intention of treating serious conditions.
Due to the successful Phase II trial and the Fast Track
Program, Encenicline has become the first alpha 7 drug
candidate to reach the Phase III trial.
Advancements in Diagnosing
Schizophrenia
A
conducted experiment indicates that eye movement tests can
demonstrate whether or not a person has schizophrenia.
Researchers from Scotland, Germany, and the U.S. analyzed
participants by using modern eye tracking technology. EyeLink
or EyeLink 1000 were the equipment utilized on a control group
and a group of participants who had schizophrenia.
The EyeLink equipment
focused on testing visual patterns, such as looking at a
moving object for 20 seconds and focusing on one stationary
object. Different images were viewed by participants to see if
they had expressive or neutral faces. The eye tests were
proven successful by diagnosing 98% of the participants
correctly.
Participants retook the
test after nine months, and the reliability of the technology
and patient diagnosis remained the same. Scientists analyzed
the results, which showed that participants with schizophrenia
had a lower performance for the visual tests compared to the
control group.
A study was published by
researchers from Columbia University, the New York State
Psychiatric Institute, and IBM's T.J. Watson Research Center.
A computerized speech analysis program was used to assist in
diagnosing if someone has schizophrenia. An advantage of using
this program is that it can pick up signs from a participant
that a researcher or physician might accidentally miss. One of
these signs is referred to as a jarring disruption, where a
person doesn’t get the entire meaning across in conversation
and jumps from sentence to sentence.
Researchers developed a
formula to determine when jarring disruptions occur throughout
a person’s speech.The formula
measured coherence and two syntactic indicators during a
person’s speech, including the length of a sentence and how
many clauses are taken.By
analyzing an individual’s speech skills, doctors have a
specific target in order to determine if a person may develop
the disease. Researchers discovered the computer program
functioned better than other technologies, such as
neuroimaging and EEG recordings of brain activity. Using
computers to analyze an individual’s speech patterns can be
another mechanism to prevent schizophrenia from developing in
the first place.
Technology for Treatments
Increasing evidence exists explaining that computer assisted
programs can help people overcome some symptoms of
schizophrenia. Researchers from the University of Cambridge
developed an iPad game called Wizard to help improve an
individual’s episodic memory.
A study was conducted on
22 test subjects with schizophrenia. The participants were
split into two groups, where the cognitive training group
played the game Wizard for 8 hours over four weeks and the
control group continued with their normal routines. At the end
of the study, the patients' improvements were measured with
the Cambridge Neuropsychological Test Automated Battery
(CANTAB) PAL and the Global Assessment of Functioning (GAF)
scale.Researchers analyzed the
test results and discovered that the cognitive training group
had better cognitive skills than the control group and overall
had higher scores on the GAF scale. While researchers are
still searching for a medicinal cure to schizophrenia,
developing games geared towards cognitive functions may assist
in retrieving memory skills of a person diagnosed with the
illness.
Conclusion
There has been a significant amount of research and
experiments conducted to discern why individuals have
schizophrenia. Scientists and companies used mice models and
stem cell research to advance research efforts. Drugs, such as
Encenicline and ITI-007, are currently in development with the
intention of becoming available to patients in the near
future.
Utilizing technology for
diagnosis and treatment may be effective new approaches to
assist individuals with schizophrenia. Research and
development tax credits are available to companies and
scientists who utilize modern technology and processes to
research and test schizophrenia.
