New developments for the treatment of muscle spasticity after stroke and nervous system defects

Chronic muscle spasticity after nervous system defects like stroke, traumatic brain and spinal cord injury, multiple sclerosis and painful low back pain affect more than 10% of the population, with a socioeconomic cost of about 500 billion USD. Currently, there is no adequate remedy to help these suffering people, which generates an immense medical need for a new generation antispastic drugs.

András Málnási-Csizmadia, co-founder of Motorpharma Ltd. and professor at Eötvös Loránd University in Hungary leads the development of a first-in-class drug candidate co-sponsored by Printnet Ltd. MPH-220 directly targets and inhibits the effector protein of muscle contraction, potentially by taking one pill per day. By contrast, current treatments have low efficacy and cause a wide range of side effects because they act indirectly, through the nervous system.

“We receive desperate emails from stroke survivors, who suffer from the excruciating symptoms of spasticity, asking if they could participate in our research. We work hard to accelerate the development of MPH-220 to alleviate these people’s chronic spasticity,” said Prof. Málnási-Csizmadia.

The mechanism of action of MPH-220 and preclinical studies are recently published in Cell. Dr. Máté Gyimesi, CSO of Motorpharma Ltd. highlighted: “The scientific challenge was to develop a chemical compound which discriminates between skeletal and cardiac muscle myosins, the motor proteins of these contractile systems. This feature of MPH-220 makes it highly specific and safe.”

Prof. James Spudich, co-founder of Cytokinetics, MyoKardia and Kainomyx, all companies developing drugs targeting cytoskeletal components, is also very excited about MPH-220 as a possible next generation muscle relaxant. “Cytokinetics and MyoKardia have shown that cardiac myosin is highly druggable, and both companies have potential drugs acting on cardiac myosin in late phase clinical trials. Skeletal myosin effectors, however, have not been reported. Motorpharma Ltd. has now developed a specific inhibitor of skeletal myosin, MPH-220, a drug candidate that may reduce the everyday painful spasticity for about 10% of the population that suffers from low back pain and neurological injury related diseases,” said Professor Spudich, former chair of Stanford medical school’s Biochemistry department, a Lasker awardee.

Drug development specifically targeting myosins is becoming a distinguished area, as indicated by last week’s acquisition of MyoKardia by Bristol-Myers Squibb Co. for 13.1 billion dollars in an all-cash deal, in the hope of marketing their experimental heart drug targeting cardiac myosin. This business activity shows the demand for start-up biotech companies such as Myokardia or Motorpharma.

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Coronavirus: Physical distancing may help ease burden on hospitals, but only to a point

Scientists have found that longer periods of social distancing alone are not successful when it comes to slowing COVID-19 spread, an advance which may help make better decisions in countries where a second wave of the pandemic is expected.

“Conventional wisdom was, the more intense and long-term the social distancing, the more you will curb the disease spread,” said Rajan Chakrabarty, a co-author of the study from Washington University in St. Louis in the US.

According to the study, published in the journal Chaos, any strategy that involves social distancing requires other steps be taken in tandem.

“But that is true if you have social distancing implemented with contact tracing, isolation and testing. Without those, you will give rise to a second wave,” Chakrabarty said.

Payton Beeler, another co-author of the study, noted that if social distancing is the only measure taken, it must be implemented extremely carefully in order for its benefits to be fully realized.

Their epidemiological model used data gathered by Johns Hopkins University in the US between March 18 and March 29, a period marked by a rapid surge in COVID-19 cases and the onset of social distancing in most US states. Calibrating the model using these datasets allowed the authors to analyse unbiased results that had not yet been affected by large-scale distancing in place, they said.

The model also included details on how much people of different age groups interact, and how that affects the spread of transmission.

“Had social distancing been implemented earlier, we probably would’ve done a better job,” Chakrabarty said.

Over the short-term, more distancing and less hospital demand go hand in hand, the scientists said, adding that this is only up to two weeks. After that, they said the time spent distancing does not benefit hospital demand as much. Society would have to increase social distancing time exponentially in order to see a linear decrease in hospital demand, the researchers noted.

They said this leads to diminishing returns. Society would see smaller and smaller benefits to hospital demand the longer it spent social distancing, the scientists explained.

According to the researchers, if social distancing “alone” is to be implemented longer than two weeks, a moderate shut down, say between 50-70 per cent, could be more effective for the society than a stricter complete shut-down in yielding the largest reduction in medical demands.

Another strategy for flattening the curve involves acting intermittently, alternating between strict social distancing and no distancing to alleviate the strain on hospitals, the study noted. According to the model, the most efficient distancing- to- no-distancing ratio is five to one, meaning one day of no distancing for every five days at home. Had society acted in this way, the researchers said the hospital burden could have been reduced by 80 per cent. “Bending the curve using social distancing alone is analogous to slowing down the front of a raging wildfire without extinguishing the glowing embers,” said Chakrabarty.

“They are waiting to start their own fires once the wind carries them away,” he said, adding however that his team’s model cannot inform strategies going forward as it used data collected in March. But Chakrabarty added that it may be able to inform our actions if we find ourselves in a similar situation in the future.

“Next time, we must act faster, and be more aggressive when it comes to contact tracing and testing and isolation,” Chakrabarty said.

(This story has been published from a wire agency feed without modifications to the text. Only the headline has been changed.)

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Disparities in stroke care at urban vs. rural hospitals impacts quality of care, patient survival

People living in rural areas are less likely to get the most advanced treatments for stroke and are more likely to die in the hospital than those treated for stroke at hospitals in urban areas, according to new research published today in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

“There are so many challenges facing rural America right now—higher rates of chronic disease, poverty and joblessness—and cardiovascular and other health outcomes are much worse in rural areas. This study shines light on one area where changes in care, such as the introduction of telehealth or other programs, could really make a difference,” said Karen E. Joynt Maddox, M.D., M.P.H., senior author of the study and assistant professor of medicine at Washington University School of Medicine in St. Louis, Missouri.

Researchers examined national data on more than 790,000 adults (the majority over age 64, 53% female) hospitalized with stroke between 2012-2017, from the National Inpatient Sample (NIS) database, the largest publicly available, all-payer inpatient health care database in the U.S. Compared with patients living in urban areas, stroke patients treated at rural hospitals were:

  • about half as likely to receive clot-busting medication (such as intravenous alteplase) to treat clot-caused strokes;
  • about one-third less likely to undergo a procedure (such as an endovascular thrombectomy) to remove a stroke-causing clot; and
  • more likely to die of any type of stroke before leaving the hospital (6.87% vs 5.82%), with no improvement in the rural-urban disparity over the 5-year period.

“The magnitude of the differences in risk of death and the lack of improvement over time were striking. One would think that recent improvements in technology and in telehealth would mean that we could, as a system, deliver optimal care no matter where people live. That turns out to not yet be the case for stroke care,” Joynt Maddox said.

As well as their lack of access to advanced therapies, rural patients also had significantly lower rates of access to specialists.

“The lack of access to specialists is often a limiting factor in adequate care for rural stroke patients, and in this case, that could mean a neurologist to guide the initial care, an interventional neurologist or radiologist to do a procedure, or having a neurosurgeon available for backup in case of any complications,” said Gmerice Hammond, M.D., M.P.H., first author of the study and a cardiology fellow at Washington University School of Medicine in St. Louis, Missouri. “Clinicians need to work to improve access to high-quality stroke care for individuals in rural areas. That means partnerships between hospitals for rapid transfer, as well as telehealth when appropriate. And clinical leaders and policymakers should prioritize improving access, care and outcomes for stroke in rural communities.”

Meanwhile, residents in rural areas can take steps to protect themselves. “Be aware of signs and symptoms of stroke, and seek care urgently if any symptoms develop. To the extent possible, be as aggressive as you can with preventive efforts like blood pressure control. The best way to survive a stroke is to not have one in the first place,” Hammond said.

According to the American Stroke Association, the most common symptoms of stroke are known as F.A.S.T., face drooping, arm weakness, speech and time to call 9-1-1. Bystanders should call 911 for immediate help even if the symptoms go away.

The study was limited in not having information on the severity of stroke or on factors that determine who is eligible for advanced therapies (such as the size of clot, where it is located, and the length of time between the onset of stroke and the patient arriving at the hospital).

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