11 months ago

Matt Might’s personal quest sparks UAB precision medicine revolution

For Dr. Matt Might, director of the Hugh Kaul Precision Medicine Institute at the University of Alabama at Birmingham, the future of medicine revolves around physicians harnessing information on a scale unimagined by patients today.

“Data is the greatest drug of the 21st century,” said Might, who discovered a rare genetic disorder affecting his young son. “In terms of impact, I don’t think any drug will outperform data in overall ability to improve and extend human life.”

Of course, doctors already rely on detailed patient information when making diagnoses and creating treatment plans. But tomorrow’s medicine, as envisioned by Might, elevates and expands the power of the information at their command.

By combining medical knowledge with computational analysis and new techniques such as genomic sequencing, physicians will be able to create customized, data-driven treatments for individual patients rather than follow protocols for attacking a certain disease.

“One of the key things to understand in precision medicine is that it is actually easier to treat a patient than a disease,” Might said. “When you are treating a disease you have to find something that works for every patient with that disease.

“If you’re treating a patient, you just have to find out what works for them. That can be very, very different.”

Powerful new tools

Might, who advised President Barack Obama on precision medicine and turned down Harvard and other suitors before coming to UAB in July 2017, believes these new tools will forever change the way physicians provide care once they are widely adopted.

Genetic testing is already helping unravel medical mysteries, especially when it comes to diagnosing rare diseases. But it will play a greater role in the future, when oncologists can routinely sequence the genome of a tumor to see if its mutations call for a specific medicine, Might said.

Already at UAB, doctors can examine a mental health patient’s DNA for clues about how he or she will respond to particular antidepressants, allowing them to rule out medications that would be less effective or cause side effects.

In addition, physicians will be able to tap into a bottomless well of knowledge. Might has collaborated with other researchers to develop an artificial intelligence agent called MediKanren that can search more than 25 million published papers for insights that can pinpoint new treatment options for puzzling medical conditions.

“Everything in medicine is changing as a consequence of the data available and the computational power to analyze that data. This is definitely a pivotal moment, a sea change moment. Medicine is not going to look the same in 10 years,” he said.

Despite his enthusiasm for precision medicine, Might never set out to become a leader in the field. In fact, at the time his voyage started, he was pursuing a career as a computer scientist, working on projects such as cybersecurity and programming languages for supercomputers.

He was also dad to a newborn son, Bertrand, born in December 2007.

The ‘diagnostic journey’

Bertrand was just 2 months old when Might first noticed a problem. His son’s movements were uncontrolled rather than circular and fluid, as they should have been. Four months later, Bertrand’s pediatrician agreed that something was wrong – he just didn’t know what it was.

At that moment, Might and his wife, Cristina, embarked on what he calls a “four-year diagnostic journey.” Over time, Bertrand’s problems multiplied. Full-blown seizures. Movement disorder. Developmental delay. And, strangely, he couldn’t cry tears.

Might was determined to solve the mystery. Eventually, Duke University scientists performed genetic sequencing on Bertrand and his parents to see if they could detect a mutation driving the youngster’s problems.

The results pointed to a malfunctioning NGLY-1 gene, which produces an enzyme needed to break down certain abnormal proteins as part of a recycling process in the body.

“Almost no one had heard of NGLY-1. It didn’t exist as a disease. It barely existed as a known gene. That gene had never been linked to human health in any way, shape or form,” Might said.

Thus, a rare genetic disorder known as NGLY-1 deficiency was discovered. Bertrand was “patient zero.” That meant doctors told Might there was little that could be done for his son until more patients with the condition were identified.

In 2012, Might published a blog post called “Hunting Down My Son’s Killer” that described Bertrand’s symptoms. It received widespread attention. Within weeks, patients began popping up all over the world, enabling research into the condition to begin.

At home, Might struggled with how to help his son.

Using his background as a computer scientist, he set up a computational analysis to identify compounds that might be useful to treat Bertrand’s condition. He quickly found 70, including 14 already approved by the FDA.

At one point, additional testing showed that Bertrand’s condition had triggered a deficiency of N-acetylglucosamine, a readily available glucose derivative. Might purchased some and, after testing it on himself, began giving it to his son.

Days later, Might noticed tears rolling down Bertrand’s face. For the first time, he had discovered a remedy to help his child. Critically, the tears halted the corneal erosion that threatened Bertrand with eventual blindness.

Other discoveries followed. Using MediKanren, Might learned that research indicated a common supplement, sulforaphane, could counter a certain molecular function triggered by NGLY-1 deficiency.

“Sulforaphane is abundant in broccoli, but not abundant enough. You’d need about 60 pounds of broccoli a day. Most fifth-graders don’t eat their own body weight in broccoli each day, but you can get it in a pill form that is highly concentrated. So he has been on that for about two months now, and for me, I think it is definitely making a difference.”

Might is now investigating whether some of the movement disorder aspects of Bertrand’s condition are similar to Parkinson’s and looking into whether treatments for that disease might benefit his son.

“I think, at last, we are moving on all fronts for Bertrand. We’re addressing seizures, eyes, movement disorders and development with this large cocktail of drugs we’ve assembled for his condition,” he said.

Creating an ‘algorithm’

Might is using the lessons he learned in his quest to help Bertrand to scale up the precision medicine initiative at UAB, using what he’s dubbed the “algorithm of precision medicine.”

At its core, the approach centers on harvesting every bit of data about a patient. Genomic sequencing is an important component because it provides a peek into the patient’s unique molecular makeup. But even information contained on a Fitbit or Apple watch can be part of the mix.

Computational technologies and deep reasoning tools such as MediKanren add a new dimension.

“We’re beginning to bring computation into medicine in a very serious way,” Might said. “Previously, it’s been largely used in a superficial way. Now we’re looking at it from more of a big data optimization perspective.”

At the Hugh Kaul Institute, made possible by a $7 million philanthropic gift in 2015, Might and his team maintain a focus on rare diseases through precision therapeutics, acting as what he calls a “clinic of last resort” for patients interested in engaging in targeted research to advance therapies for their disorders.

The institute, which has a staff of nearly a dozen, can provide physicians searching for treatment options with a research report containing recommendations personalized for an individual patient.

Precision oncology is a specific UAB focus. In one case, a genomic scan of a patient’s prostate tumor revealed mutations more consistent with ovarian cancer. Physicians were able to successfully treat the patient with medicines used to treat that form of cancer, Might said.

“Cancer is one of those things where precision medicine is the answer. Every cancer is unique,” he added. “You always need an individually tailored treatment. If you really want to treat cancer right, you’ve got to treat every cancer like a rare disease. That’s the key.”

Might sees the components of precision medicine flowing across all medical disciplines at UAB, expanding until its tactics become the standard of care for all patients.

“At UAB, we’re in the process of making everything precision medicine so that one day it won’t be precision medicine, it will just be medicine,” he said.

This story originally appeared on the University of Alabama System’s website.

Courtesy of Alabama Newscenter

4 hours ago

Tuberville on China, coronavirus: ‘We’ve got to worry about Alabama and this country’ right now

Former Auburn University football coach Tommy Tuberville is taking a different stance on China than his Republican primary runoff competitor, former U.S. Attorney General Jeff Sessions.

In an appearance on Talk 99.5’s “Matt and Aunie Show” Thursday morning, Tuberville was asked about what he thought was happening with China.

He responded, “Well, we can’t worry about China right now. We’ve gotta worry about Alabama and this country.”

Experts agree that the novel coronavirus originated somewhere around the city of Wuhan in China, and the country spent several weeks trying to obscure the extent of the outbreak. There have since been significant indications that the death toll in China is higher than the country is publicly reporting.

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Sessions has called for an extensive investigation into the communist government that runs China, and blasted the current leadership there, calling it an “evil regime.”

“You know, I hear about all these people hollering for investigations and we always investigate,” commented Tuberville on Thursday, before later adding, “[Congressional committees] investigate and nothing ever comes of it, so right now we’ve gotta worry about this country. ‘Cause right now we’re in trouble.”

In tweets responding to the Tuberville interview, Sessions said, “China’s where the virus is from, and their deliberate lies hid the danger & resulted in a pandemic that never should’ve happened! We must take on China NOW and WIN, not run scared like Tommy Tuberville!”

Later in the interview, Tuberville praised President Donald Trump’s efforts to shift the United States’ economic relationship to China.

“They’re gonna be knocked to their knees, and they should be,” the former coach said.

Paul Shashy, Tuberville’s campaign manager, said in a statement to Yellowhammer News, “If Jeff Sessions was too afraid to stand up to Robert Mueller, how can we ever expect him to stand up to China? Like President Trump, Coach Tuberville believes we should focus all of our resources on ending the Coronavirus pandemic, fixing our economy, and helping the Alabamians who need help now. Once that’s done, he’ll stand with the president to hold the Chinese fully accountable, unlike Jeff Sessions, who voted with Ted Kennedy and John Kerry to reward China with permanent trade status.”

Tuberville and Sessions will face each other at the ballot box on July 14 in the Republican primary runoff.

Henry Thornton is a staff writer for Yellowhammer News. You can contact him by email: henry@yellowhammernews.com or on Twitter @HenryThornton95.

6 hours ago

Ivey issues ‘stay-at-home’ order for the state of Alabama effective Saturday afternoon

MONTGOMERY – Governor Kay Ivey has issued a “stay-at-home” order for the state of Alabama as coronavirus (COVID-19) cases and deaths continue to rise.

The order is effective beginning Saturday, April 4, at 5:00 p.m. and will expire Thursday, April 30, 2020 at 5:00 p.m. CT.

Exceptions apply for essential activities and businesses.

The order can be read here.

An updated supplemental State of Emergency can be read here.

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Ivey made the announcement at a press conference Friday at 4:00 p.m. CT alongside State Health Officer Scott Harris, Attorney General Steve Marshall and the Reverend Cromwell A. Handy of Montgomery’s Dexter Avenue Baptist Church. Reporters were able to attend and ask questions live afterwards while following social distancing guidelines.

In a statement, Lt. Governor Will Ainsworth said he supports the stay-at-home order.

“I agree with Gov. Ivey’s decision to issue a stay-at-home order throughout Alabama, and though many may find it inconvenient, her action is the best method of combatting and controlling the spread of COVID-19 in our cities, towns, and communities,” he said.

“Alabamians have always shown courage in a crisis, so at this critical time, the best way we can stand together is by staying apart,” Ainsworth concluded.

Ainsworth’s full statement can be read here.

Ivey said in her remarks that it became obvious to her Thursday afternoon that more must be done to flatten the curve.

The governor advised she was “convinced our previous efforts to reduce social interaction [had not been enough].”

“That’s why we are taking this more drastic step,” she added.

Ivey cited the jump in confirmed cases the state experienced Thursday, along with cell phone location data made available by a national data company, as sources of information she found relevant in making her decision.

“April stands to be very tough, and potentially very deadly,” warned Ivey.

The governor said that Alabama should expect a surge in hospitalizations that she estimates will peak in 2-3 weeks.

Harris noted the the models projecting caseload change every day.

Marshall said that intentionally violating the new order is a class-c misdemeanor.

Marshall urged law enforcement officers around the state to practice restraint in enforcing the order, only using criminal action if someone was endangering others.

Handy offered spiritual advice, quoting scripture and saying, “God is our refuge and strength, always ready to help in times of trouble, we will not fear when earthquakes come and mountains tumble into the sea.”

The order allows churches to meet, as long as the crowd in the building does not exceed 10 people. “Drive-in” worship services are also allowed.

The order supercedes those made locally by counties like Jefferson and Mobile, but they both retain the ability to implement more stringent restrictions if they wish, according to Harris.

Jefferson County’s health officer indicated in a public appearance that he would likely be implementing stricter requirements for his jurisdiction, which has the highest concentration of COVID-19 patients in Alabama.

You can watch the State’s press conference below:

This story is breaking and will be updated.

Henry Thornton is a staff writer for Yellowhammer News. You can contact him by email: henry@yellowhammernews.com or on Twitter @HenryThornton95.

7 hours ago

Alabama’s budgets will face real issues post-coronavirus

Every American is fixated on the current coronavirus pandemic. It dominates local and national news, daily talk radio and Alabama’s major newspapers three days a week.

The Alabama political press is busy using this to accuse Governor Kay Ivey of wanting Alabamians to die because she hasn’t issued a “shelter-in-place” order. To their credit, usually, it’s Alabama’s budget cuts, low taxes, taxes on food, failure to expand Medicaid or abortion bans that are being used as an implement of murder by their target of the day, so give them credit for creativity.

If we as a state look past this healthcare issue and look at the damage it is already doing to the state’s economy, we will see a bunch of major issues on the horizon.

When State Senator Arthur Orr (R-Decatur) appeared on WVNN Friday morning, he talked about budgeting issues that will definitely be of major concern when the state is back open for business and the legislature resumes its budgeting process.

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Orr, who has chaired both the General Fund and Education Trust Fund committees, said that the next legislative session will be a hard one with hard fiscal choices.

Planned pay raises for teachers and other state employees are gone. Orr noted that the budgets that are passed will be “level-funding” — or close to it — and hard choices will have to be made.

But that “pain” may be short-term, not that the reverberation of the coronavirus pandemic won’t last for years. There could be long-term issues as well.

The Retirement System of Alabama has long been a hot-button in this state.

Orr sounded the alarm on the viability of the system, saying, “The RSA is among, if not the most, highly exposed defined benefit, public defined benefit plan in the country to equities or to the stock market.”

He noted, “When the stock market has tanked 30 plus percent, RSA feels a much larger hit than other retirement funds. It’s going to be a concern.”

My takeaway:

With a defined benefit payout and few opportunities to increase revenue. the actuarial tables will take a beating as the stock market slides.

Most expect the market to rebound eventually, but Orr has been talking about the RSA’s vulnerabilities for years. And this will not help.

Even if you aren’t a beneficiary of the Retirement System of Alabama, you will still feel the impact if its finances continue to head south. Orr warned of a stark reality where “taxpayers will be ending up having to pay more for retirement for all the government employees.”

Obviously, no one is thinking about this right now, but we will be revisiting this in the very near future and the impact of this could go on for a very long time.

Listen:

Dale Jackson is a contributing writer to Yellowhammer News and hosts a talk show from 7-11 am weekdays on WVNN.

7 hours ago

Survey: 50% of small businesses cannot survive more than two months of coronavirus restrictions

The National Federation of Independent Business (NFIB) Research Center on Friday released its latest survey detailing the impact of the coronavirus (COVID-19) pandemic on small businesses across the country.

The survey was conducted March 30 and utilized a random sampling of the organization’s 300,000 members. This garnered 1,172 usable responses, all small employers with 1-465 employees.

Unfortunately — but also unsurprisingly, the survey showed continued overall deterioration in the small business sector since the NFIB’s previous similar survey, which was conducted on March 20. A release from NFIB on Friday stated, “The severity of the outbreak and regulatory measures that cities and states are taking to control it are having a devastating impact on small businesses.”

In the latest survey, 92% of small employers said they are negatively impacted by the pandemic, up from 76% saying the same just 10 days prior.

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The latest survey also showed 3% of small employees answering that they are positively impacted by the coronavirus outbreak. NFIB explained that these select firms are likely experiencing stronger sales due to a sharp rise in demand for certain products, goods and services. That effect will likely wane in the coming weeks as consumers feel more secure about their personal supply levels, NFIB added.

State-specific survey data was unavailable, but NFIB Alabama State Director Rosemary Elebash said in a statement, “Without a doubt, the coronavirus has taken a tremendous toll on Alabama’s small businesses. Our members are determined to get through this, and they’re working to apply for Paycheck Protection Program loans and other forms of financial relief so they can avoid layoffs and having to close the doors for good.”

Lt. Governor Will Ainsworth (R-AL) noted, “We have organized an Emergency Small Business Task Force to identify problems our businesses are facing during this difficult time. We need to bring clarity to issues and government orders that are often confusing and to effectively communicate solutions and direct business owners to resources that can help. NFIB is an indispensable member helping to guide this task force.”

RELATED: State Rep. Whitt on coronavirus restrictions: ‘Our small businesses are getting destroyed’

Among negatively impacted small employers in the NFIB survey, 80% reported slower sales, 31% reported experiencing supply chain disruptions and 23% reported concerns over sick employees.

One other major point in the survey pertained to how long can small businesses can continue to operate under current conditions.

With the pandemic projected to continue for weeks, it is especially concerning that approximately half of small employers said they can survive for no more than two months. About 15% of small employers responded that they cannot last even another month.

Mitigation is ongoing, however. Due to escalating financial stress on the sector, more small businesses are now talking with their bank about financing needs than was the case 10 days ago. Approximately 29% of small employers have talked with someone at their bank or with the Small Business Administration (SBA) about finance options, and another 23% are planning to do so soon. A total of 38% of small employers have not, and do not, intend to do so, per NFIB’s survey.

Read the full survey here.

RELATED: University of Alabama program helps connect small businesses with federal relief funds

Sean Ross is the editor of Yellowhammer News. You can follow him on Twitter @sean_yhn

7 hours ago

Alabama automakers lend a helping hand in COVID-19 battle

Alabama automakers are stepping in to aid their communities in the fight against the COVID-19 pandemic, including support of crucial testing services and production of protective face shields for healthcare workers.

Toyota’s Huntsville engine factory is producing 7,500 protective face shields for local hospitals.

In addition, the plant has donated 160 safety glasses to local hospitals, along with $25,000 to the United Way of Madison County to support COVID-19 relief efforts.

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“With our plant idled, Toyota Alabama is eager to contribute our expertise and know-how to help quickly bring to market the equipment needed to combat COVID-19,” the company said in a statement today.

Similar efforts are also happening at Toyota facilities nationwide.

Other Alabama automakers are offering community support as well.

Hyundai Motor America and its Hyundai Hope On Wheels program have donated $200,000 to the University of Alabama at Birmingham to help expand community testing efforts.

The grant will support the existing drive-through testing site in downtown Birmingham and help other sites in Jefferson County provide much-needed screening, said UAB Medicine CEO Will Ferniany.

“Support like this gift from Hyundai Hope On Wheels helps our frontline medical staff understand that they are not alone in this fight,” he said. “This grant will help further UAB’s commitment to providing access to communitywide testing.”

The grant will also be used to expand access for pediatric-specific testing services. About 20 percent of the downtown testing site’s patient population is age 25 and under, and officials from UAB Medicine, the UAB Department of Pediatrics and Children’s of Alabama hope to continue to expand testing for this group.

Nationwide, Hyundai is donating $2.2 million to support drive-thru testing centers at 11 children’s hospitals throughout the U.S.

Hyundai Hope on Wheels supports families facing pediatric cancer, and the company said the pandemic is a particular risk to children with cancer who have compromised immune systems.

Hyundai operates an auto assembly plant in Montgomery, which has been idled amid the outbreak, as have other auto assembly plants in the state.

Honda’s plants across the U.S. are also helping out during the crisis, including its factory in Talladega County.

Honda has pledged $1 million to food banks and meal programs across North America. Plants also are donating equipment, including N95 face masks, to healthcare providers, deploying 3-D printers to manufacture visors for face shields and investigating ways to partner with other companies in producing equipment.

In Tuscaloosa County, the Mercedes-Benz plant has donated N100 reusable filters,  protective suits and other supplies to local hospitals, as well as $5,000 to the DCH Foundation to help with the hospital’s curbside testing process.

Mercedes is also working with the Alabama Department of Commerce on ways the company or its supplier network can support making parts for the medical industry, and it is providing expertise to other manufacturers that are producing healthcare supplies.

The automaker also hosted a LifeSouth community blood drive that received about 95 donors.

(Courtesy of Made in Alabama)