May 17, 2020

Tismoo's pioneerism on personalized therapeutic perspectives for Autism Spectrum Disorder

Annual World Autism Awareness Day
Alysson Muotri
Donovan Herbster
7 min
Tismoo's pioneerism on personalized therapeutic perspectives for Autism Spectrum Disorder
This week is celebrated the Ninth Annual World Autism Awareness Day. Every year, on April 2, autism organizations around the world celebrate the day wit...

This week is celebrated the Ninth Annual World Autism Awareness Day. Every year, on April 2, autism organizations around the world celebrate the day with unique fundraising and awareness-raising events. 

Autism is a complex syndrome that affects three important areas of a person's development: communication, socialization and behavior. It still has no cure and can present itself at several different levels of impairment. Though No person has yet being cured from Autism, according to many studies and researches done so far, we can no longer assume that its cure is unviable. So, in a sense, saying that autism is incurable would be misleading and unrealistic; and senior author and associate professor in the UC San Diego departments of Pediatrics and Cellular and Molecular Medicine, founder of Tismoo,Alysson Muotri, PhD,  agrees with it.

Dr. Muotri founded Tismoo as the first laboratory in the world exclusively devoted to genetic analyzes centered on personalized therapeutic perspectives for Autism Spectrum Disorder and other neurological disorders of genetic origin such as Rett Syndrome, Timothy Syndrome, Fragile X Syndrome, Angelman Syndrome And Phelan-McDermid Syndrome and the Zika Virus, amongst many others.

Tismoo began its activities with the aim of bringing the techniques and studies of the forefront, previously restricted to the universities, and put them into practice for the clinical benefit of the individuals affected by these conditions. Its goal is to recreate in the laboratory the stages of neural development from the patient's own cells - "mini-brains" - capable of capturing the genetic material of each individual.

The “mini-brains”, have gained global prominence in the media.
Built with induced pluripotent stem cells derived from patients with a rare, but devastating, neurological disorder, have helped a lot in the search to understand diverse syndromes and diseases, besides the autism, identifying a drug candidate that appears to “rescue” dysfunctional cells by suppressing a critical genetic alteration.

As published on the Molecular Psychiatry magazine, the neurological disorder is called MECP2 duplication syndrome and it was first described in 2005, being caused by duplication of genetic material in a specific region of the X chromosome that encompasses MECP2 and adjacent genes. The disorder displays a wide variety of symptoms, among them low muscle tone, developmental delays, recurrent respiratory infections, speech abnormalities, seizures, autistic behaviors and potentially severe intellectual disability. It is heritable, but can also occur randomly. MECP2 duplication syndrome occurs almost exclusively in males, but a similar disorder known as Rett (RTT) Syndrome, which involves MECP2 gene deletions, primarily affects females. Current treatment is largely symptomatic, involving therapies, drugs and surgeries that address specific issues.

As in previous, ground-breaking research with Rett Syndrome patients, Dr. Muotri, and colleagues took skin cells from MECP2 duplication patients, converted them into induced pluripotent stem cells (iPSC), and then programmed the stem cells to become neurons that recapitulate the disorder more robustly than existing mouse models.

 “Analyses of the iPSC-derived neurons revealed novel molecular and cellular phenotypes, including an over-synchronization of the neuronal networks. Interestingly, these phenotypes go in a direction opposite of what scientists had previously reported for Rett syndrome, suggesting that the correct gene dosage is important for homeostasis in human neurons," said the doctor, “But More importantly,” he continued,” the finding with human neurons helped direct the next stage, a drug screening, which uncovered a drug candidate – a histone deacetylase inhibitor that reversed all the MECP2 alterations in the mutant neurons, with no harm to control neurons." He continued.

“This work is encouraging for several reasons,” highlighted Dr. Muotri, “First, this compound had never before been considered a therapeutic alternative for neurological disorders. Second, the speed in which we were able to do this. With mouse models, this work would likely have taken years and results would not necessarily be useful for humans.”

"The great advantage of this kind of process is that we begin to open up a viable possibility for drug testing, without using the patient himself as a guinea pig. By using these 'mini-brains' it is possible to test the types and quantities of drugs and thus define a more appropriate treatment for each individual, "explains Dr. Muotri, currently considered one of the world's leading experts on autism.

In the midst of innumerous equipment, the “transdiciplinar” Tismoo’s lab, located, in Torrey Pines, at the University Of California San Diego (UCSD), also counts with the help of couple of notorious machines, such as, a multi-electrode which allows Dr.Alysson Muotri’s team of researchers to listen to the “mini-brains” electric activity when a culture of neurons is placed on a plaque. 

Besides the multi-electrode, Tismoo also uses an ingenious and contemporary electric microscopic, where it’s possible to observe synapses as they occur with the use of a fluorescent “marker”, considering, of course, that these electric impulses are not visible to the naked eye.  “It’s somewhat, alike Astronomy”, humored the neuroscientist, “When you look at the sky you don’t get to see the stars, in their entirety, right away. You’d need to enhance the signal so that the stars can be studied; the same happens in our brains. Once you can observe that snapshot, you are able to quantify the amount of synapses and how they’re formed. We’re able to witness it over time; we watch these cultures since their primordial moments, when they’re very immature, until they expand their complexity and increase the number of synapses that can be performed.”

Another remarkable apparatus is a morphometric analysis microscope, which allows the scientists to analyze in detail the anatomy of a neuron, to the point of being able to measure its dendrites, ramifications, and nucleus. It was using this technology that Dr. Muotri was able to scrutinize, for the first time, that the neurons on autism patients had a much different morphology, stagnating their growth in a given development period, which prevented these neurons from achieving maturity,  and thus, not becoming able to do as many synapses as healthy neurons. “In a normal development, you can see that synapses’ complexity increase, which causes to shape a huge variety of human behavior that we use to communicate and relate ourselves to the world; whereas the neurons with autism does not experience the same, just like if these same neurons were simply blocked”- Dr. Alysson Muotri elaborated - “The accuracy of these equipment also permit  our research to even further our tests with some pre-established substances which we believe that would enable these neurons to advance their growth passing their stagnation point, watching it over time for their effectiveness.”

The neuroscientist also suggested that his research could help finding the cure for Schizophrenia and other psychiatric diseases as well, “What we realize is that when we repair the number of synapses, it ends up repairing the communication networks formed by the neurons. My point of view is even more comprehensive: that any genetic disease, whose problem is in the synapse, we will be able to correct at some point.”

"I believe we are facing significant challenges today, as in the case of Autism. We need new business models that are able to intelligently reconcile the interests of their investors to a greater purpose and provide positive and sustainable change in society "This is what we are living at TISMOO today and it is our motivation for the new challenges that are to come," concludes Muotri.

Dr. Alisson Muotri has more than impressive credentials. He graduated in Biological Sciences from the State University of Campinas (Unicamp) in 1995, and received his PhD in Genetics from the University Of São Paulo (USP) in 2001, and is a postdoctoral fellow in Stem Cells and Neurosciences by the Salk Research Institute in La Jolla, USA, becoming professor of the University Of California School Of Medicine in 2008. His research uses stem cells to understand the development and evolution of the human brain and he pioneered the use of human embryonic stem cells, creating the first chimeric animal with human neurons. It also warned the global scientific community about the contamination of animal products in these cells. The neuroscientist also developed the first cellular model to study autistic neurons, signaling a possible reversal of the condition through new drugs with the research being published in high-impact scientific journals such as Nature and Cell. Dr. Moutri has received several international awards, including the prestigious Director's New Innovator Award from the National Institutes of Health (NIH), USA.

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Jun 11, 2021

How UiPath robots are helping with the NHS backlog

6 min
UiPath software robots are helping clinicians at Dublin's Mater Hospital save valuable time

The COVID-19 pandemic has caused many hospitals to have logistical nightmares, as backlogs of surgeries built up as a result of cancellations. The BMJ has estimated it will take the UK's National Health Service (NHS) a year and a half to recover

However software robots can help, by automating computer-based processes such as replenishing inventory, managing patient bookings, and digitising patient files. Mark O’Connor, Public Sector Director for Ireland at UiPath, tells us how they deployed robots at Mater Hospital in Dublin, saving clinicians valuable time. 

When Did Mater Hospital implement the software robots - was it specifically to address the challenges of the pandemic? 
The need for automation at Mater Hospital pre-existed the pandemic but it was the onset of COVID-19 that got the team to turn to the technology and start introducing software robots into the workflow of doctors and nurses. 

The pandemic placed an increased administrative strain on the Infection Prevention and Control (IPC) department at Mater Hospital in Dublin. To combat the problem and ensure that nurses could spend more time with their patients and less time on admin, the IPC deployed its first software robots in March 2020. 

The IPC at Mater plans to continue using robots to manage data around drug resistant microbes such as MRSA once the COVID-19 crisis subsides. 

What tasks do they perform? 
In the IPC at Mater Hospital, software robots have taken the task of reporting COVID-19 test results. Pre-automation, the process created during the 2003 SARS outbreak required a clinician to log into the laboratory system, extract a disease code and then manually enter the results into a data platform. This was hugely time consuming, taking up to three hours of a nurse’s day. 

UiPath software robots are now responsible for this task. They process the data in a fraction of the time, distributing patient results in minutes and consequently freeing up to 18 hours of each IPC nurse’s time each week, and up to 936 hours over the course of a year. As a result, the healthcare professionals can spend more time caring for their patients and less time on repetitive tasks and admin work. 

Is there any possibility of error with software robots, compared to humans? 
By nature, humans are prone to make mistakes, especially when working under pressure, under strict deadlines and while handling a large volume of data while performing repetitive tasks.  

Once taught the process, software robots, on the other hand, will follow the same steps every time without the risk of the inevitable human error. Simply speaking, robots can perform data-intensive tasks more quickly and accurately than humans can. 

Which members of staff benefit the most, and what can they do with the time saved? 
In the case of Mater Hospital, the IPC unit has adopted a robot for every nurse approach. This means that every nurse in the department has access to a robot to help reduce the burden of their admin work. Rather than spending time entering test results, they can focus on the work that requires their human ingenuity, empathy and skill – taking care of their patients. 

In other sectors, the story is no different. Every job will have some repetitive nature to it. Whether that be a finance department processing thousands of invoices a day or simply having to send one daily email. If a task is repetitive and data-intensive, the chances are that a software robot can help. Just like with the nurses in the IPC, these employees can then focus on handling exceptions and on work that requires decision making or creativity - the work that people enjoy doing. 

How can software robots most benefit healthcare providers both during a pandemic and beyond? 
When the COVID-19 outbreak hit, software robots were deployed to lessen the administrative strain healthcare professionals were facing and give them more time to care for an increased number of patients. With hospitals around the world at capacity, every moment with a patient counted. 

Now, the NHS and other healthcare providers face a huge backlog of routine surgeries and procedures following cancellations during the pandemic. In the UK alone, 5 million people are waiting for treatment and it’s estimated that this could cause 6,400 excess deaths by the end of next year if the problem isn’t rectified.

Many healthcare organisations have now acquired the skills needed to deploy automation, therefore it will be easier for them to build more robots to respond to the backlog going forwards. Software robots that had been processing registrations at COVID test sites, for example, could now be taught how to schedule procedures, process patient details or even manage procurement and recruitment to help streamline the processes associated with the backlog. The possibilities are vast. 

The technology, however, should not be considered a short-term, tactical and reactive solution that can be deployed in times of crisis. Automation has the power to solve systematic problems that healthcare providers face year-round. Hospital managers should consider the wider challenge of dealing with endless repetitive work that saps the energy of professionals and turns attention away from patient care and discuss how investing in a long-term automation project could help alleviate these issues. 

How widely adopted is this technology in healthcare at the moment?
Automation was being used in healthcare around the world before the pandemic, but the COVID-19 outbreak has certainly accelerated the trend.  

Automation’s reach is wide. From the NHS Shared Business Service in the UK to the Cleveland Clinic in the US and healthcare organisations in the likes of Norway, India and Canada, we see a huge range of healthcare providers deploying automation technology. 

Many healthcare providers, however, are still in the early stages of their journeys or are just discovering automation’s potential because of the pandemic. I expect to see the deployment of software robots in healthcare grow over the coming years as its benefits continue to be realised globally. 

How do you see this technology evolving in the future? 
If one thing is certain, it’s that the technology will continue to evolve and grow over time – and I believe there will come a point in time when all processes that can be automated, will be automated. This is known as the fully automated enterprise. 

By joining all automation projects into one enterprise-wide effort, the healthcare industry can tap into the full benefits of the technology. This will involve software robots becoming increasingly intelligent in order to reach and improve more processes. Integrating the capabilities of Artificial Intelligence and Machine Learning into automation, for example, will allow providers to reach non-rule-based processes too. 

We are already seeing steps towards this being taken by NHS Shared Business Service, for example. The organisation, which provides non-clinical services to around two-thirds of all NHS provider trusts and every clinical commissioning organisation in the UK, is working to create an entire eco-system of robots. It believes that no automation should be looked at in isolation, but rather the technology should stretch across departments and functions. As such, inefficiencies in the care pathway can be significantly reduced, saving healthcare providers a substantial amount of time and money. 

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