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.
