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3 years ago

Alabamians’ stunning research places sickle cell cure within reach: ‘We’re working day and night’

UAB Stem Cell Institute research lab for DNA and genome research may be on the way to curing sickle cell disease. (Meg McKinney/Alabama NewsCenter)
UAB Stem Cell Institute research lab for DNA and genome research may be on the way to curing sickle cell disease. (Meg McKinney/Alabama NewsCenter)

By: Bob Blalock

Tim Townes has a dream. He has a dream that one day in Alabama, he will see four little girls sitting on the steps of the Sixteenth Street Baptist Church in Birmingham.

Townes dreams that on Martin Luther King Jr. Day two years from now, national television news shows will trumpet the story of those girls, healthy and no longer ravaged by sickle cell disease. He dreams of seeing that kind of good news on an important civil rights anniversary – instead of well-worn footage of the Sixteenth Street bombing in 1963 that killed four little girls, or marchers beaten on Selma’s Edmund Pettus Bridge.

“I think Alabamians could really be proud of that and I think would want to work toward that,” says Townes, a Ph.D., director of the UAB Stem Cell Institute and chairman of the Department of Biochemistry and Molecular Genetics.

Townes’ most audacious dream may be that his lab cures sickle cell disease, an inherited blood disorder that affects nearly 100,000 Americans and their families. Most people with sickle cell disease are of African ancestry (about 1 in 365 African-American babies in the U.S. is born with sickle cell disease, according to the National Institutes of Health) but it also affects people from Hispanic, southern European, Middle Eastern and Asian-American backgrounds.

“I just think it’s going to be done somewhere within two years. Why not in Alabama?” Townes says. “We’re working day and night to make it happen.”

Townes and his researchers appear to be tantalizingly close to curing sickle cell disease and potentially many others. In September, they published in the journal Cell Reports that they have corrected the genetic mutation that causes Severe Combined Immunodeficiency. (SCID is often called “Bubble Boy” disease after David Vetter, a Texas boy who lived for 12 years in a specially built “bubble” because his immune system did not work.) Like sickle cell disease, SCID is caused by a single defective base pair of the 3 billion present in human DNA.

CRISPR-Cas9 technology

Townes’ team took skin cells from a SCID patient at Children’s of Alabama who received a bone marrow transplant, converted those cells into stem cells and used what is known as CRISPR-Cas9 technology to target and correct the mutated base pair.

With CRISPR, a molecule of RNA that matches the targeted region of DNA steers the Cas9 protein, which acts like microscopic scissors that snip out the mutation.

“What we’ve done is now modified the system so that it is safer, so it cuts only in the right place,” Townes says. “We want to correct the mutation, but not change something somewhere else.”

With the SCID patient’s cells, the team showed that the corrected cells function as they should.

“So if those cells had been transplanted back into the patient, they would have cured the disease,” Townes says.

Science fiction

UAB Stem Cell Institute could be on the verge of a cure for sickle cell disease. (Meg McKinney/Alabama NewsCenter)
UAB Stem Cell Institute could be on the verge of a cure for sickle cell disease. (Meg McKinney/Alabama NewsCenter)

Dr. Fred Goldman, a professor of Pediatrics at UAB, director of the Lowder Pediatric Blood and Marrow Transplantation Program at Children’s of Alabama and a member of the research team, says: “It sounds sort of science fiction-like but it really isn’t. It’s actually happening right now.”

It won’t happen in patients, though, unless the U.S. Food and Drug Administration gives Townes, Goldman and team approval to conduct clinical trials to prove their approach is safe and that it works. Townes says they will apply for FDA permission before the end of the year.

“We’d like to submit by December of this year and start a trial by December of next year,” Townes says. “There are patients out here suffering unbelievably.”

Townes says sickle cell disease is first on the list because all patients have the same mutation in a single base pair of DNA. As well, he has studied sickle cell for more than three decades and is determined to find a cure.

“I tell people I’ve been here 31 years and had this goal for that long and they say, ‘Well, why haven’t you already done it?’ We hoped we could do it long before this, but the fact is nobody else in the world has done it,” Townes says.

While Townes says they’d like to use their gene-editing technology on sickle cell sufferers “tomorrow … we realize we have to prove safety.”

“The Food and Drug Administration is fairly conservative and they should be to make sure these new technologies, especially when they’re genetic technologies where we’re changing genes, that it is safe and effective, and safety comes first,” he says.

Proving safety

A key to proving safety is to show that the gene-editing technology affects only the single mutated base pair of DNA and nothing else. If it can be used safely in people, gene editing could cure “a whole host of other diseases,” Goldman says.

Townes adds: “I think the excitement is that it really could change the way that you do medicine because the applications are enormous.”

Townes and Goldman say the technology potentially could be used to cure many blood disorders and autoimmune diseases caused by a genetic mutation in a single site, similar to sickle cell disease and SCID. There also may be a way to apply the technology to prevent or inhibit the inflammation that accompanies Parkinson’s and Alzheimer’s diseases, which “could dramatically change” how those diseases progress, Townes says.

One potential complication, though, is the fear among many scientists that gene editing with the CRISPR-Cas9 technology has risks that aren’t well understood and require thorough research.

“Considerations include the possibility of off-target alterations, as well as on-target events that have unintended consequences,” a group of prominent scientists including Nobel Prize winner David Baltimore wrote in the April 3 issue of Science. “At present, the potential safety and efficacy issues arising from the use of this technology must be thoroughly investigated and understood before any attempts at human engineering are sanctioned, if ever, for clinical testing.”

When asked about the group’s concerns, Townes notes that in the September Cell Reports paper, “We performed whole genome sequencing and demonstrated no off-target effects and no unintended on-target effects. We have also demonstrated the same fidelity in sickle patient cells.” (Whole genome sequencing is the genetic map of a person.)

Further, Townes says his team has no plans to use CRISPR-Cas9 technology “to modify the germ line” – in layman’s terms, creating “designer babies.”

“Although we think that modification of the germ line would be safe, there are difficult ethical considerations about making decisions that affect multiple generations,” he says.

Townes’ most immediate concern is moving quickly to receive FDA approval for clinical trials that could provide relief for sickle cell sufferers. “We want to do it for these families,” he says.

The red zone

UAB is looking for a cure for sickle cell disease at a genetic level. (Meg McKinney/Alabama NewsCenter)
UAB is looking for a cure for sickle cell disease at a genetic level. (Meg McKinney/Alabama NewsCenter)

After driving toward a cure for the disease for so many years, Townes, who played football at the University of Tennessee in the early 1970s, says his team has reached the “red zone” – inside the opponent’s 20-yard line.

“Of course, you can get in the red zone playing a football game and run into difficulties scoring,” he says. “It takes a lot of work to get in the red zone. We’ve been driving for a long time, and now we want to convert.”

Townes’ lab is one of many all over the world pushing toward developing new technologies for understanding, treating and curing genetic diseases. He likens the work to assembling a 10,000-piece puzzle.

“Everyone’s putting in pieces of the puzzle and we’ve put in pieces already and many other people have,” he says. “Somebody has to put in the last piece, and there’s nothing wrong with wanting to put in the last piece.

“And so that’s what we’re pushing to do. We want to cure sickle cell disease here in Alabama. We want to develop a treatment for Severe Combined Immunodeficiency right here in Alabama,” Townes says. “There’s no reason that we can’t do that.”

(Video below: UAB’s Stem Cell Institute research team discusses their work)

About sickle cell disease

Sickle cell disease is the most common genetic disorder in the United States, according to the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). UAB Stem Cell Institute Director Tim Townes says it is also one of the most misunderstood diseases.

People with sickle cell disease have abnormal hemoglobin, a protein in red blood cells that carries oxygen through the body. Normal red blood cells are disc-shaped and flexible, which allows them to flow through even the smallest blood vessels.

In people with sickle cell disease, abnormal red blood cells are shaped like a crescent, or sickle, and stiff. As a result, the sickle-shaped cells can clog blood vessels, slowing or even stopping the flow of blood. That prevents oxygen from reaching nearby tissue and can cause severe pain as well as infections, major organ damage and stroke. The severity of the disease varies widely from person to person, with a life expectancy of about 40-60 years, according to the NIH.

The only cure for sickle cell disease is to transplant bone marrow stem cells from a normal donor to a patient. The best chance for success is using a sibling donor, yet the odds of finding a perfect sibling match are less than 15 percent, according to Dr. Fred Goldman, who directs the Blood and Marrow Transplantation Program at Children’s of Alabama and treats sickle cell and SCID patients.

“If there are no matched siblings, the next best option would be to use a perfectly matched unrelated donor. However, many times we are not able to locate such a donor, and in addition, complications from transplant are much higher using unrelated donors,” Goldman says. “Everyone is working very hard to make bone marrow transplant safer, but we believe using a patient’s own bone marrow that has been ‘corrected’ with CRISPR-Cas9 technology will offer the best chance for success with the fewest side effects.”

About 1,000 children and 5,000 adults in Alabama suffer from sickle cell disease, Goldman says.


This story originally appeared on the Alabama NewsCenter
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8 hours ago

Regions latest to withdraw from BCA

Regions Financial Corp. became the latest company to withdraw its membership from the Business Council of Alabama. According to a story in the Montgomery Advertiser, the company formally notified BCA leadership of their intentions today.

This decision from one of the state’s largest employers comes on the heels of Alabama Power’s withdrawal from the business organization on Monday.

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Both companies had privately expressed concerns about the BCA’s leadership and direction. Their decisions to end long-standing relationships with the BCA mark a turning point in their collective effort to strengthen the business community’s approach to economic development and job growth.

BCA Chairman Perry Hand acknowledged for the first time on Monday that Billy Canary was, in fact, now the outgoing President of the group. In a letter made public by Hand, he detailed that Canary’s tenure would end sometime prior to the start of next year. The departing companies identified the uncertainty surrounding that transition as a significant contributing factor to their leaving.

In addition to BCA’s failure to settle on a timely and decisive transition plan, the companies also expressed concern over the group’s effectiveness and financial health. The Yellowhammer Multimedia Executive Board has itself explored some of these same issues facing BCA.

Regions Financial Corp. is a multi-state bank based out of Birmingham. According to its website, it is the only Fortune 500 company headquartered in Alabama and has $123 billion in assets.

Allison Ross is the owner and publisher of Yellowhammernews.com.

9 hours ago

Tuscaloosa Mayor Walt Maddox says he’s pro-life, but his language is chock-full of pro-choice phraseology

Earlier this month the Democrat Party’s nominee for governor, Walt Maddox, responded to a questionnaire about his views on many issues facing Alabamians, but his answers about abortion proved to be the most revealing, although probably unintentionally.

The Tuscaloosa mayor began by writing that he was “personally opposed to abortion,” a slippery term if there ever was one, before proceeding to use similar phrases that we normally hear from the pro-choice crowd.

It’s as if Maddox was sampling lines from an abortion apologist’s Greatest Hits album.

Why this matters: Alabama already has one pro-choice politician in high office with Sen. Doug “20 Weeks” Jones, who infamously voted against banning aborting unborn children when they’re 20-weeks old and capable of feeling pain. We cannot afford to have another one.

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The questionnaire was formulated by the editors of Yellowhammer News and our partners over at the Alabama Policy Institute. Here’s the rather straight-forward question on abortion:

“Alabama has four abortion clinics operating across the state, and Planned Parenthood has announced plans to build a new clinic in downtown Birmingham. How do you feel about these clinics and what would you do as governor about any taxpayer funds they receive?”

And here was the mayor’s answer, which as you can read isn’t really an answer at all:

“I’m a pro-life Democrat who is concerned that many Republicans are more pro-birth than pro-life,” Maddox wrote. “Perhaps Sister Joan Chittister best summed up my feelings when she said “I do not believe that just because you’re opposed to abortion, that that makes you pro-life. In fact, I think in many cases, your morality is deeply lacking if all you want is a child born but not a child fed, not a child educated, not a child housed. And why would I think that you don’t? Because you don’t want any tax money to go there. That’s not pro-life. That’s pro-birth. We need a much broader conversation on what the morality of pro-life is.”

He continued. “Although I am personally opposed to abortion, under the law of the land a woman has a right to choose up until the point of fetal viability,” he wrote. “The federal Hyde Amendment prohibits use of federal funds to pay for abortions except those that endanger the life of the woman, or that result from rape or incest, and Alabama law does not provide any state funds for abortions. The courts will ultimately decide which of Alabama’s several laws regulating abortion are constitutional, including any restrictions on new abortion clinics. As a governor sworn to uphold the federal and state constitutions and the laws of Alabama, I will faithfully execute Alabama’s laws within the constitutional limits defined by the Supreme Court.”

Here’s a breakdown of Maddox’s pro-choice phraseology:

— “Republicans are more pro-birth than pro-life.” 

I’ve seen this same line in dozens of emails from pro-choice activists after every pro-life column I publish. 

It’s like clockwork. They can’t cope with keeping the focus on abortion because the act is indefensible, so they attempt to change the subject entirely with what they hope is a witty turn of phrase. 

But it’s not witty. It’s hollow, and betrays the hollowness of both their argument and the moral framework it’s built upon. 

The two issues — abortion and welfare — are two entirely different subjects. But in their world, it must be OK to end someone’s life if the state isn’t willing to provide for it financially (which we do for the truly needy, by the way).

— “Although I am personally opposed to abortion, under the law of the land a woman has a right to choose up until the point of fetal viability.”

Maddox is trying to have it both ways here, but this isn’t that sort of issue. If he believes an unborn child is a person, which I suppose forms the basis for his personal opposition to abortion, then any measure of morality would compel him to oppose it completely. 

The unborn child is either a living person or not, and if so, it’s life must be defended as anyone else’s life would be defended.

To believe that, personally, yet do nothing to stop it from happening means one is either a coward or creature of such unscrupulous ambition as to be wholly undeserving of public office.

— “The courts will ultimately decide.”

No, the people will, at least in the end.

But to the point: here Maddox evades the core question by falling back on courts, as if the governor has no role. As if nobody has a role but five of nine lawyers on the Supreme Court. But we’re not living in a judicial tyranny, at least not yet. 

There are many things the governor can do — sign pro-life bills into law, make executive decisions about funding certain abortion providers, and use the bully pulpit to encourage greater action.

It seems as if Maddox might not be willing to do any of those things, preferring to toss the hot potato over to the courts.

Fundamentally, this is weakness. I’m sure one could have heard an argument similar to Maddox’s in the 1850s: “Although I am personally opposed to slavery, under the law of the land a white man has a right to own a black man. So …”

Then he quotes Sister Joan Chittister, a Catholic nun, in what he may think is some sort of clever nod to faith. 

But conservative Catholics would see straight through this, too, because Sister Joan disagrees with Catholic teaching on abortion. She’s effectively pro-choice because she has said that she opposes it as a primary form of birth control but leaves room for abortion in many other situations, which makes her opinion on the matter decidedly not Catholic at all. 

The fact that of all the people he could quote, Maddox quotes a nun who disagrees with the Catholic teaching on abortion is very revealing.

Perhaps one of his staffers wrote the response, allowing their pro-choice phraseology to seep into the answers. Maybe he would have said more if given more space and time.

If it’s sincerely held, Maddox should stand strong on his personal opposition to abortion. We need more people who share his beliefs to step forward, to convince others, and to help put an end to the awful practice. 

Yellowhammer News would happily publish a guest post by Maddox should he wish to further explain his beliefs about abortion, and we’d hope such an explanation would dispense with wordy obfuscation and answer our inquiry more directly — since he is opposed to abortion, what would he do to stop abortions from happening in Alabama?

Until such an explanation is offered, Alabamians should remain very skeptical of Maddox’s views on abortion, and certainly his ability to represent a state whose citizens are overwhelmingly pro-life.

@jpepperbryarsis the editor of Yellowhammer News and the author of American Warfighter

10 hours ago

Far out: Univ. of Alabama astronomer helps discover a new type of black hole

Astronomy news is always old news because of, you know, light years and such.

About 750 million years ago, in a galaxy far, far away (queue the Star Wars intro), a black hole consumed a nearby star in an event that has revealed to astronomers the existence of something new: a mid-sized black hole.

Dr. Jimmy Irwin, an associate professor of astronomy at the University of Alabama who is part of the team that discovered this new type of black hole, explained the revelation in an interview with Yellowhammer News.

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Astronomers have established with good evidence the existence of “low-mass” black holes, which are judged to be between 3 and 30 times more massive than the sun, as well as “super-massive” black holes, one of which has been discovered in our own galaxy to be 4 million times more massive than the sun.

“We know that low-mass black holes form and we know that high-mass black holes form,” Dr. Irwin explained, “but between these two book ends, it’s not clear whether there’s a mechanism in nature that allows black holes to be formed with, say, a mass above one hundred times the mass of our sun and below one million times the mass of our sun.”

There’s pretty good evidence now, though, that such medium-sized black holes do exist.

As Dr. Irwin explained, when a black hole rips up and consumes a star, its debris becomes very hot and emits x-ray radiation, creating data that becomes observable over time.

“There’s already a built-in time lag, based upon the distance of the object,” Irwin said.

The observations that led to this discovery were made through what Dr. Irwin described as a detective-like process.

The astronomer who began the project, Dr. Dacheng Lin, was actually a post-doctoral researcher under Irwin in years past. Dr. Lin began looking back at data recorded by a variety of telescopes in Europe and the United States between 2003 and 2006 and discovered an observable change at a particular spot in this far-away universe.

“There was a bright x-ray source in one observation and it was dimmer in the next one,” Irwin explained.

“Piecing together the history he was able to discover that this probably happened, or at least this radiation reached the earth’s telescopes, probably sometime in 2003,” he said.

Irwin stressed that we’ve known about black holes for a long time, but not of this type.

“This idea of stars being torn apart isn’t a new idea,” he said. “What’s new is that we’re seeing stars ripped apart by one of these mid-sized black holes.”

@jeremywbeaman is a contributing writer for Yellowhammer News

10 hours ago

Rep. Roby: Combatting the opioid crisis at home and across the country

There are countless important issues currently facing our state and nation. From our ongoing conversations with North Korea to the continuing need for enhanced security at the southern border, there’s no shortage of priorities that warrant discussion. Unfortunately, there is one very serious issue that continues to make headlines: the horrific opioid epidemic that is gripping our state and the entire country.

I’m sure most of us know someone whose life has been affected by opioid abuse. Whether it’s prescription pain relievers or synthetic opioids like fentanyl, the crisis has only gotten worse. 64,070 people died from overdoses in our country in 2016, and 756 of those individuals were Alabamians. Now, in 2018, the problem has not improved. Did you know that 115 people in the United States die after overdosing on opioid drugs every single day? Just this year alone, it is estimated that more than 2 million Americans will suffer from opioid addiction.

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I’m pleased that last October, President Trump declared the opioid crisis a public health emergency. This epidemic has been wreaking havoc on communities and families across our country for far too long. While the statistics are certainly shocking, this is about so much more than numbers. Hundreds of thousands of real American people with lives, careers, and families have lost the battle with opioid drug abuse. That’s why the House has made combating this crisis a top priority over the last several years.

You may remember that back in 2016, Congress passed the Comprehensive Addiction and Recovery Act and the 21st Century Cures Act. Earlier this year, we provided $4 billion in government funding specifically to address the opioid crisis. Building upon this work, the House recently passed dozens of meaningful bills to further combat the opioid epidemic, and I’d like to share the four ways we are using this legislation to help fight this serious issue.

First, with the recently passed legislation, the House is focusing on treatment and recovery. Our bills improve and expand access to treatment and recovery services, provide incentives for enhanced care, and establish comprehensive opioid recovery centers. Hundreds of thousands of Americans from all walks of life are currently trapped by addiction, and it is imperative that we provide the resources to treat their addiction and help them recover.

Second, we’re aiming for prevention. Opioids are an important part of modern day medical care for pain treatment, but they are prescribed entirely too often – and at alarming rates. Our legislation addresses these high prescribing rates while enhancing prescription drug monitoring programs. We have the technology, and it’s past time we used it to more effectively address this crisis. Our legislation also encourages non-addictive opioid alternatives, when practical, to treat pain, and improves the data that allows us to identify and help at-risk patients before the problem becomes dangerously serious.

Third, we’re making efforts to better protect communities of all sizes throughout the country by giving law enforcement the tools necessary to remove dangerous drugs. Our bills also enable us to better intercept illicit opioids at international mail facilities and improve access to federal resources for local communities.

Last but certainly not least, we’re fighting fentanyl. The legislation we passed in the House allows us to better tackle these ever-changing synthetic drugs, crack down on foreign shipments of illicit drugs, and provide grants for communities to combat fentanyl that is destroying lives as we speak.

I am proud of the efforts we’ve made in the House recently to press forward in our fight against this horrible crisis gripping our state and nation, but our work is far from complete. We owe it to the more than 40,000 Americans who die every year – and their families – to push on until strong progress is made. You can read more about our work to combat the opioid epidemic by visiting www.opioidcrisis.gop.

U.S. Rep. Martha Roby is a Republican from Montgomery.

11 hours ago

‘Moderate’ Doug Jones continues to prove he is just another liberal on immigration

Senator Doug Jones’ views on immigration seem to line up more with California Senator Kamala Harris than they do with Alabama voters. He has endorsed Harris’ long-shot attempt to end “child separation” at the border as a standalone bill.

He has also taken to Twitter to publicly blame President Trump for the entire problem:

These aren’t really new positions by Senator Jones.

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In an American Immigration Council article by Melissa Cruz, she points out his views, which are very clear over his career:

“Jones opposes construction of the Trump administration’s U.S.-Mexico border wall

“Jones did not support the termination of the Obama-era Deferred Action for Childhood Arrivals (DACA) initiative”

“Jones favors upgrading the immigration system. Specifically, he has proposed reassessing the current quota system, as well as looking at potential overhauls to the administrative procedures for immigration.”

“If we can make a more streamlined process of allowing immigrants into this country legally…” Jones said, “we would have far less undocumented immigrants.”

“Jones publicly spoke out against HB 56—then considered the harshest anti-immigrant law in the country—and reiterated that position throughout his campaign.”

Why this matters:

No one believes Senator Jones would be in D.C. if it was not for the fact that the Republicans nominated a completely destroyed dumpster fire named Roy Moore.

The selling point by Alabama’s political press was that “Jones isn’t even that liberal”, a tactic they are using with Walt Maddox as well.

The problem for Jones is that eventually votes will have to be cast and positions will have to be taken.

The reality is Jones is wildly out of step with most Alabamians and every passing day will expose that.

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