Hope For Lanie: Curing SMA

Hope For Lanie: Curing SMA

CREATED Apr 17, 2014

DALLAS (Ivanhoe Newswire) – She may be in a wheelchair, but 14-year-old Lanie Hannah doesn't let that stop her from having fun.

She has SMA. It attacks the body's motor neurons and causes paralysis.

"It affects my daily life, like not being able to do certain things," she told Ivanhoe.

"Put her in bed, take her out of bed, dressing, I mean it affects everything that she does," Lana Hannah, Lanie's mom, told Ivanhoe.

There is no cure for SMA but for the first time doctors are studying an experimental therapy that targets more than just symptoms, it targets mutated SMN genes, which are responsible for SMA.

"With this treatment, we are targeting the disease," Susan T. Iannaccone, MD, Pediatric Neurologist, Children's Medical Center in Dallas and UT Southwestern Medical Center, told Ivanhoe.

The gene therapy is injected into the spinal fluid. The idea is the drug will enter into the nerve cells and change the protein production so that the normal SMN gene is created. It could mean fewer symptoms and more strength for patients.

"Our hope, absolutely, is that someday these children will not experience the symptoms," Dr. Iannaccone said.

Lanie was in the phase I trial. She hopes this therapy will be the answer she's been waiting for, because she has big plans for the future.

"I want to go to college. I want to be a teacher, and I want to teach English," Lanie said.

"Everything that she does amazes me," Lana Hannah said.

Lanie has a milder form of the disease, but she has never been able to walk. Researchers say the next step is to study more patients in a phase II trial to see if the gene therapy does what they hope it will.


BACKGROUND: Spinal Muscular Atrophy (SMA) is a genetic disease of the anterior horn cells, which are located in the spinal cord. SMA affects the voluntary muscles for activities such as crawling, walking, head and neck control and swallowing. Patients are usually diagnosed with SMA before six months of age. One in 5,000 babies is born with SMA. About 80 percent of SMA patients have the severe form of the disease and, without ventilators, do not usually live past age 2. The disease mainly affects the muscles closest to the trunk of the body. Weakness in the legs is generally greater than weakness in the arms. Some SMA patients may experience abnormal movements of the tongue -- called tongue fasciculations. However, most SMA patients experience normal senses, feelings, and intellectual activity. In fact, patients with SMA are often exceptionally intelligent and sociable. SMA is an autosomal recessive disease, which means both parents must carry the specific gene responsible for the disease. If both parents carry the gene, they have a 25 percent chance of having a child with SMA. (Source:http://www.fsma.org/fsmacommunity/understandingsma/)

NEW TECHNOLOGY: Generally doctors have treated SMA in a proactive way by trying to maintain movement when possible and being proactive in protecting children from other illnesses that could come with SMA. SMA in part is due to a malfunctioning protein, called Antisense oligonucleotide. The protein can change a way a gene functions. So now, doctors are treating SMA by targeting the protein. A gene therapy is injected into the spinal fluid, where it travels through the spinal tissue and into the nerve cells affected by SMA. Once there it tries to correct the malfunctioning protein so that the normal gene is created. Although not a cure, the therapy should make the patient stronger. The therapy is currently in the trail stage, and is only being tried on patients between the ages of 2 and 14. (Source: Dr. Susan Iannaccone)


Susan Iannaccone, MD, Chief of Pediatrics Neurology at Children's Medical Center in Dallas and Professor of Pediatrics and Neurology Neurotherapeutics at UT Southwestern, talks about a new method for treating spinal muscular atrophy.

You don't hear a lot of spinal muscular atrophy, what is that?

Dr. Iannaccone: It's a genetic disease of mostly infants. It's a neurodegenerative disease that affects the motor neurons; it causes paralysis.

Is it rare when a child lives past the age of two?

Dr. Iannaccone: It's unusual. The most common form of the disease is a severe one that causes death in infancy. However, there are milder forms of the disease wherein the children survive to adulthood.

When they survive to adulthood, what is their lifelike?

Dr. Iannaccone: Many of them never walk so they use a wheelchair. They may have complication from respiratory infections, because of the weakness that causes difficulty coughing. There are some patients who can walk and walk independently throughout their life that would be the mildest form.

Does it get worse?

Dr. Iannaccone: It does, but it's different from the usual sense of a progressive disease. So SMA causes increasing weakness early in the disease, very rapidly, and then for survivors there can be very, very slow progression over many years.

I know this is all basic information, but is there lifespan shorter than if they do get to adulthood?

Dr. Iannaccone: Most patients yes, but not necessarily. The most important factor is lung infection. If the patient has normal lung function, then he should have a normal life expectancy.

How was this disease traditionally treated before this new drug?

Dr. Iannaccone: We treat complications in a proactive way.  We try to maintain mobility whether it's with assistive devices or a wheelchair. We try to prevent lung infections by a good pulmonary toilet; taking all the smokers out of the house; sometimes taking the kids out of school during flu season. Then we are very aggressive about treating any infections. If the child develops a cold we immediately institute airway clearance measures to try to prevent pneumonia. And if the child has pneumonia we don't treat at home we treat in the hospital.

But now there is gene therapy?

Dr. Iannaccone:  Yes there is an experimental therapy that could be called gene therapy.

What does that do?

Dr. Iannaccone: This is what's called Antisense oligonucleotide, which is a protein; it's a protein that is developed to change the way the gene functions; so that normal protein is produced.

So you're no long targeting the symptoms you're targeting the disease?

Dr. Iannaccone: Yes with this treatment we are targeting the disease.

How will that help the patients?

Dr. Iannaccone:  We don't know that it's going to help at all; it's experimental. It's brand new and we've only just finished a Phase I study. So at this point, we don't know that it's going to make a difference.

How does the drug work, is it an injection?

Dr. Iannaccone:  We give the drug into the back. It's injected in to the spinal fluid, which is the fluid that circulates around the spinal cord. Nerve cells that are affected by this disease are in the spinal cord, so the drug passes from the spinal fluid in to the spinal cord tissue and hopefully in to those cells.

What is the hopeful outcome?

Dr. Iannaccone: We hope that it changes the protein production so that the normal SMN protein is produced in the nerve cell.

What would that mean for the patient?

Dr. Iannaccone: If it works the patient should get stronger.

Would it cure it?

Dr. Iannaccone: We're a little conservative about using the word cure. Cure would mean you stop the disease and don't have to give any more medicine. This experimental treatment is probably something that the patient would have to receive periodically like a diabetic has to receive insulin. So it would be a treatment, but not necessarily a cure.

For this experimental drug you're giving it to two to fourteen year olds, why specifically for that age?

Dr. Iannaccone: That age was an arbitrary decision made for this particular study. The age range the criteria for patients included in a study is always arbitrary; it's based on many, many factors not just scientific factors. In most cases that decision is made by a committee or a group of people. In this particular case that was an arbitrary decision to use those ages.

Is gene therapy a wave of the future where you can have a disease and never experience the disease?

Dr. Iannaccone: Yes, the idea of gene therapy has broadened a lot in the last decade. We used to think of gene therapy as actually changing the gene, the structure of the gene, and this is a different technology that's changing the way the gene behaves. Our hope is that someday these children will not experience the symptoms and complications of their disease.

Does this give you hope after decades of looking at this?

Dr. Iannaccone: It's very gratifying. We have been working for two decades to study how this disease behaves in patients. We've worked very hard to put out standard of care recommendations so that every child with this diagnosis receives the maximum best care to prevent complications. We've worked hard with basic researchers and other people for drug development and it's really nice to see this come to fruition at this point.

What's next for this?

Dr. Iannaccone: The next step is to continue the safety study and to start looking at benefit efficacy. With the first study we only looked at safety profiles and with the next study will look at efficacy; meaning is there any effect on muscle strength.

Are there any openings available for people interested in participating in this study?

Dr. Iannaccone: At this point we have no open slots for this next study, but there will be other studies coming alone and then we'll have more slots available.

Is there any reason you would not try gene therapy on a SMA patient?

Dr. Iannaccone: We have what's called exclusion criteria. There are certain conditions under which we would not be able to enroll a patient in the study. There are a number of them, that's true for all clinical trials, there are exclusion criteria.

If this drug was approved would there be some that would be too far along to use this drug or would it only work with early intervention?

Dr. Iannaccone: That is a very important question. As to what's the window of opportunity for treating this disease; for many of them like SMA we don't know what that window of opportunity is. There has been concern that if we don't treat this early enough, like in early infancy, we might not have an effect, but the truth of the matter is, right now we don't know. There may well be a long window of opportunity for patients.


UT Southwestern Medical Center
University News Bureau