1 week 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

11 hours ago

GoFundMe raising money for fallen Auburn PD officer William Buechner

A GoFundMe has been established in memory of Auburn Police Department Officer William Buechner, who was shot and killed in the line of duty late Sunday night.

A representative of the fundraising platform has confirmed its authenticity to Yellowhammer News. The GoFundMe will establish a memorial fund to assist Buechner’s family.

While the initial goal was set at $10,000, the campaign has already blown through that benchmark in less than 24 hours, raising over $20,500 as of 5:00 p.m. on Tuesday.

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Buechner leaves behind a wife (Sara) and two children, including a one-year-old daughter.

In addition to raising funds, prayers are also being requested for the family.

Governor Kay Ivey on Monday ordered flags in Alabama to be flown at half-staff until sunset on Saturday to honor Buechner.

Sean Ross is a staff writer for Yellowhammer News. You can follow him on Twitter @sean_yhn

11 hours ago

Randall Woodfin: Alabama abortion ban could end two tech companies bids to locate in Birmingham

Since passage and being signed into law by Gov. Kay Ivey, the fallout from the new abortion ban has been harsh for many in Alabama.

Opponents of the law warned passage would not only impact Alabama’s reputation, but it could also threaten economic development opportunities for Alabama.

On Tuesday, Birmingham Mayor Randall Woodfin claimed that in fact was the case.

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Birmingham FOX affiliate WBRC reported that the abortion ban could be the reason two tech firms could take a pass on locating in Birmingham.

Woodfin did not disclose the name of the firms.

Yellowhammer News reached out to the Birmingham mayor’s office and the Birmingham Business Alliance, which functions as the metropolitan area’s chamber of commerce, about the merits of the report and is still awaiting a response.

@Jeff_Poor is a graduate of Auburn University, the editor of Breitbart TV and host of “The Jeff Poor Show” from 2-5 p.m. on WVNN in Huntsville.

12 hours ago

‘Party of no?’ Democrats block lottery bill in Alabama House, end best chance of Medicaid expansion

MONTGOMERY — SB 220, State Sen. Greg Albritton’s (R-Atmore) clean paper-only lottery bill, failed on a procedural vote in the Alabama House of Representatives on Tuesday, essentially killing the bill.

Democrats joined with hardline conservatives to stop the bill from even getting fully debated on the floor in a 53-36 vote, with one abstention. Fifty-four affirmative votes were needed (60% of those voting) on the procedural motion, meaning the lottery failed by a single vote.

Political observers were quick to note that Democrats have been pushing a lottery for the past two decades, campaigning on the right of the people of Alabama to vote via referendum on the issue. However, on Tuesday, Democrats stood in the way of that becoming reality.

The bill had been passed by the Senate but seems to be dead in the House. Observers believe this was the best chance a lottery had of getting to a referendum this quadrennium and for the foreseeable future.

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State Rep. Steve Clouse (R-Ozark) carried the bill in the House. He presented a substitute during a committee meeting last week that changed the revenue distribution in the bill so that 75% of funds would flow to the state general fund, while 25% would go to the Education Trust Fund. The committee adopted the substitute unanimously during that previous meeting. On advancing the bill itself, the only two “nay” votes in committee were Democrats.

The bill passed beforehand by the Senate did not allow for any revenue to benefit education.

Senate President Pro Tem Del Marsh (R-Anniston) has said that lottery money benefitting the general fund would protect the education fund.

The general fund has obligations that are expected to grow significantly in coming years, including Medicaid and the corrections system.

Despite the fact that the House Minority Caucus, i.e. the House Democrats, have said Medicaid expansion is their number one priority, killing the lottery bill on Tuesday ended their best chance of achieving that goal.

House Minority Leader Anthony Daniels (D-Huntsville) had a conversation with Marsh recently in which Marsh told Daniels Medicaid expansion was not possible right now because of a lack of general fund revenue to fund the expansion. However, Marsh added to Daniels that lottery revenues bolstering the general fund could make Medicaid expansion a realistic option.

On Tuesday, Democrats complained that SB 220 would not raise the maximum amount of money possible because it did not expand other forms of gaming, like slot machines, or legalize existing electronic bingo operations in places like Greene County or Macon County.

Clouse expressed that his bill would raise more revenue than the alternative, which of course is not having a lottery at all. SB 220 was projected to generate $167 million in revenue for the state annually once the lottery got fully operational.

Procedurally, SB 220 could be brought back up by the House if Democrats stop blocking the lottery legislation.

Update 4:50 p.m.:

Proponents of the lottery in the House will likely attempt the procedural motion again on Tuesday night. Only one attempt at reconsideration is allowed by the chamber’s rules.

It is important to note that 63 votes would be needed for final passage, even if the 60% of those voting threshold is met on the procedural vote.

Update 8:15 p.m.:

Clouse told reporters the lottery will not come back up on Tuesday.

State Rep. Terri Collins (R-Decatur) told Yellowhammer News that she intends to bring an amendment to the lottery legislation to make the revenue be split equally between education and the General Fund.

Daniels told Yellowhammer News that giving more of the revenue to the Education Trust Fund would not win over his party’s votes, saying their opposition is “much broader than that.”

Sean Ross is a staff writer for Yellowhammer News. You can follow him on Twitter @sean_yhn

13 hours ago

‘Real and painful consequences’: Ala. Secretary of Commerce, Toyota head ‘profoundly disappointed’ by Trump trade action

President Donald Trump has now concurred with a Department of Commerce Section 232 report that deemed imports of automobiles and automobile parts as a “national security threat,” with the president’s determination seriously worrying Alabama’s automobile manufacturing industry and economic development leaders.

The Department of Commerce report, delivered to Trump on February 17, concluded that imports of automobiles and certain automobile parts threaten to impair the national security of the United States. On Friday, Trump announced that he has completed his review of the report and agrees with its conclusion.

The president has ordered U.S. Trade Representative Robert Lighthizer to open a negotiation process with affected countries like Japan and, if agreements are not reached within 180 days, tariffs could be instituted on auto and auto parts imports from those countries.

Focusing on Japanese automobile manufacturers alone, Alabama is home to a Honda manufacturing facility in Lincoln, and the under-construction Mazda-Toyota joint venture in Huntsville features two Japanese auto giants.

In a statement on Tuesday, Akio Toyoda, who is president of Toyota and chairman of the Japan Automobile Manufacturers Association (JAMA) emphasized that he “is profoundly disappointed by President Trump’s announcement.”

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Speaking on behalf of JAMA, Toyoda said, “We are dismayed to hear a message suggesting that our long-time contributions of investment and employment in the United States are not welcomed. As Chairman, I am deeply saddened by this decision.”

“For JAMA member companies, providing the best possible vehicle options for our customers is our top priority. We now have 24 manufacturing plants, 45 research-and-development/design centers, and 39 distribution centers in 28 states, and have cumulatively invested approximately $51 billion in manufacturing facilities alone,” he outlined. “It is also important to remember that, even during the Great Recession, JAMA member companies made great efforts to maintain employment, and currently we provide more than 93,000 direct American jobs. According to a new study, a total of over 1.6 million jobs (including intermediate and spin-off jobs) in the U.S. are supported by Japanese automakers. These numbers speak for themselves about JAMA member companies’ long history of local contributions and commitment as U.S. corporate citizens, and we are certain that neither imported vehicles and parts nor our American operations ‘threaten to impair’ the U.S. national security.”

Toyoda also warned that potential moves like tariffs down the line from the United States could have major consequences for places with large auto industries like Alabama.

“Any trade restrictive measures would deliver a serious blow to the U.S. auto industry and economy, as it would not only disadvantage U.S. consumers, but also adversely affect the global competitiveness of U.S.-produced vehicles and suppress company investments in the U.S,” Toyoda advised.

He continued, “We believe that free and fair trade as well as a competitive business environment based on international rules support the global competitiveness of the U.S. auto industry, leading to consumer benefits and sustained growth of the U.S. economy.”

“JAMA member companies strongly hope that President Trump understands our desire to further contribute to the U.S. economy and employment and that the dialogue between the governments of Japan and the U.S. leads to an outcome that supports the development of the auto industries and economies of both nations,” Toyoda concluded.

In a statement to Yellowhammer News, Alabama Secretary of Commerce Greg Canfield said “the U.S. Department of Commerce’s Section 232 findings… set the stage for tariffs that threaten to seriously disrupt the operations of” the state’s auto manufacturing operations “and put Alabama jobs on the line.”

Canfield explained, “Automakers based in Europe and Japan have made profound contributions to Alabama’s economy through significant investment and job creation that has enriched families and communities. Mercedes-Benz opened a manufacturing facility in Alabama 22 years ago; today, that complex has seen nearly $6 billion in investment and is home to thousands of jobs. Between them, Honda and Toyota have invested well over $3 billion in their Alabama manufacturing operations and employ more than 5,000 people in Alabama. Toyota and Mazda are currently investing another $1.6 billion to open an auto assembly plant in Alabama with 4,000 new jobs. Auto suppliers for these automakers have also invested heavily in operations in Alabama — and they continue to do so.”

“Over the years, Alabama has formed strong partnerships with these automotive companies,” he added. “We’ve also made many lasting friendships with industry leaders, including Akio Toyoda, president of Toyota Motor Corp., who personally came to Alabama’s capital to announce the Mazda Toyota Manufacturing USA assembly plant in 2018, and the top leadership at Honda and Mercedes.”

“We regret to see these relationships imperiled by the U.S. Department of Commerce’s Section 232 findings that set the stage for tariffs that threaten to seriously disrupt the operations of these Alabama manufacturing operations and put Alabama jobs on the line. We will continue to work to help the Trump administration understand that these proposed tariffs will have real and painful consequences for many hard-working Alabamians and companies that have established roots in our state,” Canfield concluded.

Sean Ross is a staff writer for Yellowhammer News. You can follow him on Twitter @sean_yhn

13 hours ago

Conservatives and liberals should agree — it’s time to #DefundAPTV

There is a public relations crisis gripping Alabama and it must be addressed by the Alabama legislature.

The risk is so real that tourism could plummet, businesses could flee the state and educated young people could choose to move out of their home state for a more welcoming state.

A gay rat is marrying a gay aardvark and they have invited the gay rat’s third-grade students to the wedding and Alabama Public Television  (APTV) refused to carry it.

Seriously.

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Let’s ignore how unlikely it is that a teacher would invite his students to his wedding, let’s ignore that the main character wears glasses but not on his ears and let’s ignore that this is somehow an aardvark.

(Arthur/Facebook)

Let’s ignore all of that and focus on the real issues here. Should the state of Alabama be using taxpayer dollars to fund any of this?

“Arthur” already has a controversial past in Alabama. In 2005, APTV blocked another showing of the show because there was a character with two gay moms.

A Google search says, “Arthur often deals with important issues families face such as asthma, dyslexia, cancer, diabetes, and autism spectrum disorder.”

Super-edgy stuff.

But the real problem is this kind of censorship should lead to liberals demanding that the entire entity of Alabama Public Television be disbanding for refusing to show the kind of diversity they demand out of all forms of entertainment, including Marvel’s cinematic universe.

Conservatives should be demanding that we eliminate APTV altogether because there are plenty of other outlets doing the same kind of programming and there is no need for state resources to be propping up this kind of programming.

This programming is not cheap.

These resources can go somewhere else instead of fueling the culture wars that are ripping our state apart and giving us a black eye nationally.

So…

If you are a liberal, contact your legislators and demand they #DefundAPTV for daring to erase this beautiful and brave cartoon rat and aardvark’s wedding.

If you are a conservative, contact your legislators and demand they #DefundAPTV and rein in this reckless spending on programming that is attempting to brainwash our young people.

Eliminate this menace today (and get rid of Alabama Public Radio while you are at it).

(Arthur/Facebook)

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